Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions | Enfermedades Infecciosas y Microbiología Clínica (English Edition)

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Meropenem acts by inhibiting the synthesis of the bacterial cell wall, and it is indicated in the treatment of serious lung, urinary, intrabdominal, skin and soft tissue infections or meningitis, with dosage ranging from 1g every 8h to 2g in lung infections associated with cystic fibrosis or acute bacterial meningitis.<a class="elsevierStyleCrossRef" href="#bib0155">1</a>The efficacy of meropenem is correlated with the time that plasma concentrations exceed the minimum inhibitory concentration of the pathogen (T>MIC).<a class="elsevierStyleCrossRef" href="#bib0160">2</a> In carbapenems, the PK-PD objective is to achieve T>MIC during approximately 40% of the dosing interval,<a class="elsevierStyleCrossRef" href="#bib0155">1</a> though this objective has not been established in the clinical setting and studies in critically ill patients point to better clinical and microbiological results with 100% T>MIC.<a class="elsevierStyleCrossRefs" href="#bib0165">3,4</a> The carbapenem MIC breakpoint, according to the international reference organizations, will determine the sensitivity or resistance of the microorganism to the antibacterial. In order to achieve clinical cure of serious infections and prevent antimicrobial resistance, dose optimization is needed.<a class="elsevierStyleCrossRef" href="#bib0175">5</a>Meropenem 1g is usually administered by intermittent infusion (II) over approximately 30min, producing a peak plasma concentration of 50–60mg/L, which drops to 0.25mg/L after 8h.<a class="elsevierStyleCrossRef" href="#bib0155">1</a> Several studies evidence that prolonged infusions of meropenem, including extended infusion (EI) and continuous infusion (CI), provide greater likelihood of reaching the T>MIC target than standard dosage forms.<a class="elsevierStyleCrossRefs" href="#bib0180">6–9</a> CI would ideally achieve a higher T>MIC, but it has drawbacks such as permanent attachment to the line, Y-site incompatibilities, and mainly stability problems associated with carbapenems.<a class="elsevierStyleCrossRef" href="#bib0200">10</a> However, EI of 1 or 2g of meropenem each 8h stands as an effective alternative since it increases the T>MIC, avoiding the disadvantages associated with the CI. Jaruratanasirikul et al.<a class="elsevierStyleCrossRef" href="#bib0205">11</a> point out that EI would achieve the PK-PD objective of 40% T>MIC with a likelihood of 90% compared to 79% with II for doses of 0.5g/8h (MIC≤4mg/L), 1g/8h (MIC≤8mg/L) and 2g/8h (MIC≤16mg/L).To ensure that patients receive sufficient meropenem to achieve cure while avoiding exposure to toxic degradation products, chemical stability and physical compatibility of meropenem should be maintained throughout the period of administration. Stability data available until now indicate that meropenem in 0.9% sodium chloride (NS) at concentrations ranged from 4 to 20mg/mL is stable for 3–7 days at 5°C in elastomeric infusion devices for CI<a class="elsevierStyleCrossRefs" href="#bib0210">12,13</a> and that meropenem 1 or 2g in 100mL with NS (10 and 20mg/mL, respectively) is stable for 5 days at 5°C and 10h at 25°C in infusion bags for EI.<a class="elsevierStyleCrossRefs" href="#bib0210">12–14</a>The objective of the present study is to determine the chemical stability and physical compatibility of meropenem in elastomeric infusion devices and infusion bags at concentrations used in clinical practice (25 and 120mg/mL in infusors; 4 and 8mg/mL in infusion bags) at different temperatures (4.5, 24.5 or 32°C), in order to evaluate the stability of the preparation during its administration by CI or EI and the possibility of anticipated preparation of admixtures.MethodsReagents and materialsAs reagents, meropenem 1000mg powder for injection (Aurovitas Spain, Barcelona, Spain), NS in Viaflo® infusion bag (made of polyethylene, polyamide and polypropilen) of 50 or 250mL (Baxter, Barcelona, Spain), sterile water (API) for injection (B. Braun, Barcelona, Spain), acetonitrile (Scharlab, Barcelona, Spain) and sodium dihydrogen phosphate (NaH2PO4; Panreac, Barcelona, Spain) were adquired.Singleday® 2mL/h 50mL and Folfusor® LV 10mL/h 240mL (Baxter, Barcelona, Spain) elastomeric infusion devices (made of polyisoprene) and light protection bags (Diffuplast, Italy) were used.AdmixturesAdmixtures were prepared by duplicate following Good Manufacturing Practice (GMP)<a class="elsevierStyleCrossRef" href="#bib0225">15</a>, being 24 the total number of admixtures. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows dose, volume and container of the admixtures. To prepare them, meropenem powder was reconstituted with API and dilluted to the corresponding volume with NS. All admixtures were introduced in ligh protection bags.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Stability studiesChemical stability and physical compatibility of meropenem were evaluated at different concentrations and temperatures (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Admixtures in infusors were stored at 32°C, since it is the physiological temperature reached by the infusor during its administration,<a class="elsevierStyleCrossRef" href="#bib0230">16</a> and at 4.5°C because previous studies indicate that meropenem is more stable under refrigeration than at high temperatures.<a class="elsevierStyleCrossRef" href="#bib0220">14</a> Admixtures in infusion bags were also stored at 4.5°C and at 24.5°C, as room temperature during administration. The possibility of anticipated preparation was evaluated by storing admixtures at 4.5°C followed by 32°C for infusors or 24.5°C for infusion bags; time of refrigeration was greater in admixtures in infusors (12h) than in infusion bags (6h) since its preparation is more complex, takes more time and due to the high workload of nursing staff, it can be prepared during a 12-h shift. Time of study was 5–6 days for infusors and 1 day for infusion bags; the fact of evaluating chemical stability and physical compatibility for more than 1 day in infusors is that its cost is highest and the preparation is most complex so, in case of not administering the infuser to the patient, it can be reused.Chemical stability of meropenem in each admixture was determined by measuring its concentration by high performance liquid chromatography (HPLC) in an aliquot of 1mL extracted at different sampling times: just after preparation (t=0h) and at 2, 4, 8, 12 and 24h and then every 24h for 5–6 days for admixtures stored in infusors and at 2, 4, 6, 9, 12, 14 and 24h for admixtures in infusion bags.An Agilent Technologies 1100 HPLC system (Agilent Technologies Inc., Waldbronn, Karlsruhe, Germany) with a diode array detector was used for the analysis. The HPLC method was modified from Foy et al.<a class="elsevierStyleCrossRef" href="#bib0235">17</a> Chromatographic separations were achieved on a reversed phase column C18® (150mm×4.6mm inner diameter; 5μm) with a gradient of mobile phase containing 0.01M NaH2PO4 pH 2 and acetonitrile (t=0min, 93:7, v/v; t=6min, 88:12, v/v; t=16min, 51:49, v/v, respectively) at a flow rate of 0.8mL/min. Column temperature was 25°C and injection volume, 5μL; wavelength was 298nm and time of analysis, 17min. Chromatographic method was previously validated according to the International Conference on Harmonization (ICH) guidelines<a class="elsevierStyleCrossRef" href="#bib0240">18</a> and was adequate to determine meropenem in admixtures.The remaining concentration of meropenem (%RC) at each sampling time was expressed as the mean percentage and standard deviation (SD) of the initial concentration (after preparation); the initial concentration was expressed as 100%. The stability of a solution for infusion is maintained when the %RC remains >90% throughout the infusion period.<a class="elsevierStyleCrossRefs" href="#bib0245">19,20</a> So, the parameter used to define chemical stability was T90, time at which %RC was 90%.The pair data concentration-time were adjusted, if possible, to a zero- (Eq. <a class="elsevierStyleCrossRef" href="#eq0005">(1)</a>) or first-order kinetic equation (Eq. <a class="elsevierStyleCrossRef" href="#eq0010">(2)</a>). T90 was estimated by considering the time at which the 95% one-sided confidence limit for the mean curve intersects 90% of the initial concentration of meropenem:<elsevierMultimedia ident="eq0005"></elsevierMultimedia><elsevierMultimedia ident="eq0010"></elsevierMultimedia>being C, meropenem concentration at a specific sampling time; C0, meropenem concentration at t=0; K0, zero-order degradation rate constant and K1, first-order degradation rate constant; t, sampling time.Physical compatibility of each admixture was evaluated at each sampling time by measuring, in an extracted aliquot of 5mL: (i) pH, with glass electrode and pH-meter (model 3510, Jenway, UK); incompatibility if variation of pH is >5%; (ii) color changes, cloudiness (turbidity) and/or precipitation, measured by visual inspection; incompatibility if some of these parameters appear.Results<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows chemical stability and physical compatibility parameters for all the admixtures: (a) the average of %RC at the end of the study and the parameter T90; (b) the initial value of pH, time at which variation of pH was >5% and time at which the color of admixture changed; (c) expiration time, by considering chemical stability and physical compatibility.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>As regards admixtures in infusors (admixtures 1–12), the increase in temperature from 4.5°C to 32°C lead to a 64% decrease in %RC at the end of the study and significant decreases in T90 from 5 days to 14h in Singleday® 2mL/h 50mL (120mg/mL) and from 4 days to 7h in Folfusor® LV 10mL/h 240mL (25mg/mL). Similar %RC and T90 values were obtained for admixtures stored at 32°C, with and without pre-cooling. In admixtures with a concentration of meropenem of 120mg/mL (admixtures 1–4), there were variations of pH>5% from day 5at 4.5 and 32°C and visual color changes were observed earliest that in admixtures with low meropenem concentration (admixtures 7–12). So, expiration time was shorter when increasing the concentration of meropenem.In admixtures stored in Viaflo® (admixtures 13–24), %RC was ≥90% at the end of the study (1 day). Variations of pH were <5% in all cases and visual color changes were not observed. So, expiration time was at least 1 day, since it is the time of the study.<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the kinetic parameters for meropenem degradation and estimated T90 values.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionPrevious studies indicate that the stability of meropenem depends on the diluent, concentration, temperature and pH.<a class="elsevierStyleCrossRefs" href="#bib0235">17,21</a> NS is usually used as diluent since it improves stability of meropenem compared to other diluents such as glucose 5% or 10%.<a class="elsevierStyleCrossRef" href="#bib0215">13</a> Stability of meropenem in NS solution decreases with increasing concentration of meropenem<a class="elsevierStyleCrossRefs" href="#bib0235">17,21</a> and with increasing temperatures,<a class="elsevierStyleCrossRefs" href="#bib0220">14,17,21</a> being stable for a longer time under refrigeration and degrading more quickly at temperatures upper than 35°C.<a class="elsevierStyleCrossRefs" href="#bib0235">17,21,22</a> In our study, there were not statistically significant differences in %RC and T90 between admixtures in infusors with different meropenem concentration (admixtures 1–6, 120mg/mL; admixtures 7–12, 25mg/mL) but physical compatibility and consequently, expiration time were reduced at high meropenem concentration and at high temperature (32°C). The observed color changes could be a consequence of the degradation of meropenem by hydrolysis of the beta-lactam ring,<a class="elsevierStyleCrossRef" href="#bib0245">19</a> favored by high concentration and temperature; when color changes, it is recommended not to administer admixtures since physical incompatibility is usually related to loss of potency and increase in toxicity.So, the only admixture that can be administered in CI of 24h is meropenem 6g in 240mL of NS in Folfusor® LV 10mL/h 240mL as long as it is infused at 4.5°C, being expiration time of 4 days. This admixture becomes a possible alternative in Home Care Units, where EI (administration every 8h and drug withdrawal after 3–4h) is not a viable option. Several studies have proposed different ways to maintain infusors under refrigeration during its administration such as placing the infusors with frozen ice-bricks in a standard carry-bag<a class="elsevierStyleCrossRefs" href="#bib0235">17,21</a> or in a cassette attached to an infusion pump<a class="elsevierStyleCrossRef" href="#bib0260">22</a>; Grant et al. indicate that it is possible to maintain elastomeric infusion devices at 2–8°C over 24h in a cassette between two ice-bricks, which are changed every 8h, at a room temperature of 20–25°C.<a class="elsevierStyleCrossRef" href="#bib0260">22</a>Admixtures containing 1 or 2g of meropenem in 250mL of NS in Viaflo® can be used for II (15–30min) or EI (3–4h) at 4.5 or 24.5°C. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows T90 of admixtures of 1 or 2g of meropenem in 100mL and 250mL of NS at room temperature or under refrigeration. As can be observed, increasing the final volume from 100 to 250mL, chemical stability increases up to 1 day at 24.5°C, which would allow EI of meropenem 1 or 2g in 3–4h.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Consequently, as previous studies have shown in clinical practice,<a class="elsevierStyleCrossRefs" href="#bib0270">24–26</a> the fact of administering meropenem by CI or EI would increase the clinical cure rate by 30% compared to conventional administration of beta-lactams in critical or septic patients. These results are also supported by meta-analysis in critically ill patients or with infections caused by high MIC pathogens, which indicate higher clinical cure rate and lower mortality.<a class="elsevierStyleCrossRefs" href="#bib0285">27–30</a>Finally, the possibility of preparation in advance of admixtures of meropenem in NS in infusors and infusion bags was evaluated. The results obtained in this study indicated that preparation in advance is not possible in infusors for CI since after 12h stored at 4.5°C, T90 was 5h at 32°C in Singleday® 2mL/h 50mL and 2h in Folfusor® LV 10mL/h 240mL, being the time of administration to patients of 24h. Nevertheless, preparation in advance is viable in Viaflo® if storing the admixture 6h at 4.5°C and administering during the following 18h at 24.5°C, enough time not only for II (15–30min) but also for EI (3–4h).In conclusion, the administration of meropenem 6g in perfusion of 24h in 240mL of 0.9% NaCl in infusor Folfusor® LV 10mL/h 240mL could be possible if the admixture is infused at 4.5°C. This study also increases chemical stability and physical compatibility of meropenem 1 or 2g in 0.9% NaCl in Viaflo® infusion bag (250mL) to 24h, being between 3 and 10h<a class="elsevierStyleCrossRefs" href="#bib0155">1,14</a> in 100mL; therefore, extended infusion in 3–4h is also feasible, allowing its use in septic or critically patients or with high MIC Gram negative bacteria in which a higher clinical cure rate has been evidenced. Moreover, anticipated preparation of admixtures of meropenem in Viaflo® is possible, as opposed to its usual method of preparation at the time of administration because of its short stability.As a limitation on this study, the results of chemical stability and physical compatibility of meropenem obtained are applicable to infusion bags made of polyethylene, polyamide and polypropilen (Viaflo®) and infusors of polyisoprene (Singleday® and Folfusor®).Conflict of interestAuthors state no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres2039816" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1744065" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2039817" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1744066" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Reagents and materials" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Admixtures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Stability studies" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-05-31" "fechaAceptado" => "2022-07-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1744065" "palabras" => array:4 [ 0 => "Compatibility" 1 => "Stability" 2 => "Meropenem" 3 => "Infusor" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1744066" "palabras" => array:4 [ 0 => "Compatibilidad" 1 => "Estabilidad" 2 => "Meropenem" 3 => "Infusor" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionProlonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients. This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation. MethodsAdmixtures in study were: (i) meropenem 6g in 0.9% sodium chloride (NS) in infusor of 2mL/h 50mL or 10mL/h 240mL; (ii) meropenem 1 or 2g in NS in infusion bag of 250mL. Temperatures of study were: (i) infusor: 4.5°C, 32°C or 12h at 4.5°C followed by 32°C; (ii) Infusion bag: 4.5°C, 24.5°C or 6h at 4.5°C followed by 24.5°C. Time of study was 5–6 days in infusor and 1 day in infusion bag. Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection. ResultsChemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature. Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day. ConclusionAdministration of meropenem 6g in infusion of 24h in 240mL of 0.9% NaCl in infusor of 10mL/h could be possible if the admixture is infused at 4.5°C. Extended infusion of meropenem 1 or 2g in 0.9% NaCl in infusion bag (250mL) in 3–4h is also feasible. Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24h." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa infusión intravenosa prolongada de beta-lactámicos aumenta la velocidad de curación clínica comparada con la administración convencional en pacientes críticos o sépticos. Este estudio tiene como objetivo determinar la estabilidad química y la compatibilidad física de meropenem en condiciones utilizadas en la práctica clínica para evaluar la estabilidad de la preparación durante su administración y la posibilidad de la preparación anticipada. MétodosLas mezclas en estudio fueron: (I) meropenem 6g en cloruro sódico 0,9% (SN) en infusor de 2mL/h 50 mL o 10mL/h 240mL; (iii) meropenem 1 o 2g en SN en bolsa de infusión de 250mL. Las temperaturas de estudio fueron: (i) infusor: 4,5°C, 32°C o 12h a 4,5°c seguido de 32°C; (ii) bolsa de infusión: 4,5°C, 24,5°C o 6h a 4,5°c seguido de 24,5°C. El tiempo de estudio fue de 5-6 días en infusor y 1 día en bolsa de infusión. Se evaluó la estabilidad química mediante cromatografía líquida de alta resolución y la compatibilidad física por medida de pH e inspección visual. ResultadosLa estabilidad química y la compatibilidad física de meropenem en las mezclas en infusores disminuyeron al aumentar la concentración de meropenem y la temperatura. Las mezclas en bolsas de infusión mostraron estabilidad química y compatibilidad física durante al menos 1 día. ConclusiónLa administración de meropenem 6g en infusión de 24h en 240 mL de cloruro sódico 0,9% en infusor de 10ml/h podría ser posible si la mezcla es administrada a 4,5°C. La infusión extendida de 1 o 2g en cloruro sódico 0,9% en bolsa de infusión (250 mL) en 3-4h es también viable. Puede realizarse la preparación anticipada de mezclas de meropenem en bolsas de infusión con una estabilidad de 1 día." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AD: admixture; V: final volume; T: temperature; t: time of study." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose (g) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">V (mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Container \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T (°C) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">t (days) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Singleday® 2mL/h 50mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Singleday® 2mL/h 50mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Singleday® 2mL/h 50mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h at 4.5°C+32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7–8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">240 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Folfusor® LV 10mL/h 240mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">240 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Folfusor® LV 10mL/h 240mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">240 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Folfusor® LV 10mL/h 240mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h at 4.5°C+32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13–14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17–18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6h at 4.5°C+24.5°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19–20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21–22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23–24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viaflo® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6h at 4.5°C+24.5°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3382569.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Dose, volume, container, temperature and time of the study of the admixtures of meropenem." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AD: admixture; %RC: percentage of remaining concentration of meropenem±standard deviation (%); T90: time at witch %RC is 90%; d: day; h: hour; pH0, initial pH; pH variation, >5%: time at with variation of pH was >5%; color change: time at with color of admixture changed; –: without changes." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">AD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Chemical stability</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Physical compatibility</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Expiration time \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">%RC (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T90 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pH0 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pH variation >5% \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Color change \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9±1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.05±0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.8±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.97±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.0±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+5h 32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.1±0.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7–8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.2±1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.00±0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.2±2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.14±0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.1±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+2h 32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.975±0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+3h 32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+2h 32°C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13–14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96.9±0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.17±0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.240±0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17–18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.1±0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.245±0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19–20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.618±0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.235±0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21–22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.6±2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.24±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23–24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.9±0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.25±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3382566.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "%RC>90%." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Minimum 1 day." ] ] ] "descripcion" => array:1 [ "en" => "Chemical stability and physical compatibility parameters of meropenem in admixtures at the end of the study." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AD: admixture; K0: zero-order degradation rate constant; K1: first-order degradation rate constant; r2: regression coefficient, T90: time at witch %RC is 90%; –: data could not be adjusted to kinetic equations." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">A D \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Zero-order</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First-order</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">K0×10−3 (mgmL−1h−1) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">r2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T90 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">K1×10−3 (mgmL−1h−1) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">r2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T90 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130.3±15.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6777 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12±0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6935 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">760.7±17.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.6±0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">646.3±23.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.980 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+7h 32°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5±0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+2h 32°C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7–8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">176.2±8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.945 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.4±0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.988 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">294.4±10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.978 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C+6h 24.5°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.72±0.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.996 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12h 4.5°C \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3382568.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Kinetic parameters for meropenem degradation." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "PE: polyethylene; PA: polyamide; PP: polypropilen; ?: unknown; T90: time at witch %RC is 90%; d: days; h: hours; Ref.: reference; –: results obtained in the present study." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Concentration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Temperature (°C) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Infusion bag \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">T90 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ref. \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="middle">1g/100mL</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0155">1</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0265">23</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0155">1</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9–10h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0260">22</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="middle">1g/250mL</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PE, PA, PP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PE, PA, PP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="middle">2g/100mL</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0215">13</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0265">23</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21–26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0215">13</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–6h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0260">22</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="middle">2g/250mL</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PE, PA, PP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PE, PA, PP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 d<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => 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Original article

Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions

Estabilidad química y compatibilidad física de meropenem en mezclas para infusión intravenosa continua y extendida

Sara Giménez-Ginera, Antoni Llopis-Alemanya, Begoña Porta-Oltraa, Pilar Llopis-Salviaa, Mónica Climente-Martía, María Amparo Martínez-Gómezb,

Corresponding author

martinez_margoma@gva.es

Corresponding author.

a Department of Pharmacy, Doctor Peset University Hospital, Valencia, Spain

b Fundación Para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana, (FISABIO), Valencia, Spain

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    "titulo" => "Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions"
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        "autoresLista" => "Sara Gim&#233;nez-Giner, Antoni Llopis-Alemany, Bego&#241;a Porta-Oltra, Pilar Llopis-Salvia, M&#243;nica Climente-Mart&#237;, Mar&#237;a Amparo Mart&#237;nez-G&#243;mez"
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      "es" => array:1 [
        "titulo" => "Estabilidad qu&#237;mica y compatibilidad f&#237;sica de meropenem en mezclas para infusi&#243;n intravenosa continua y extendida"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Meropenem is a broad-spectrum antibiotic with bactericidal activity against Gram positive and negative bacteria&#46; Meropenem acts by inhibiting the synthesis of the bacterial cell wall&#44; and it is indicated in the treatment of serious lung&#44; urinary&#44; intrabdominal&#44; skin and soft tissue infections or meningitis&#44; with dosage ranging from 1<span class="elsevierStyleHsp" style=""></span>g every 8<span class="elsevierStyleHsp" style=""></span>h to 2<span class="elsevierStyleHsp" style=""></span>g in lung infections associated with cystic fibrosis or acute bacterial meningitis&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The efficacy of meropenem is correlated with the time that plasma concentrations exceed the minimum inhibitory concentration of the pathogen &#40;<span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> In carbapenems&#44; the PK-PD objective is to achieve <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC during approximately 40&#37; of the dosing interval&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> though this objective has not been established in the clinical setting and studies in critically ill patients point to better clinical and microbiological results with 100&#37; <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> The carbapenem MIC breakpoint&#44; according to the international reference organizations&#44; will determine the sensitivity or resistance of the microorganism to the antibacterial&#46; In order to achieve clinical cure of serious infections and prevent antimicrobial resistance&#44; dose optimization is needed&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Meropenem 1<span class="elsevierStyleHsp" style=""></span>g is usually administered by intermittent infusion &#40;II&#41; over approximately 30<span class="elsevierStyleHsp" style=""></span>min&#44; producing a peak plasma concentration of 50&#8211;60<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; which drops to 0&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;L after 8<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Several studies evidence that prolonged infusions of meropenem&#44; including extended infusion &#40;EI&#41; and continuous infusion &#40;CI&#41;&#44; provide greater likelihood of reaching the <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC target than standard dosage forms&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;9</span></a> CI would ideally achieve a higher <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC&#44; but it has drawbacks such as permanent attachment to the line&#44; Y-site incompatibilities&#44; and mainly stability problems associated with carbapenems&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> However&#44; EI of 1 or 2<span class="elsevierStyleHsp" style=""></span>g of meropenem each 8<span class="elsevierStyleHsp" style=""></span>h stands as an effective alternative since it increases the <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC&#44; avoiding the disadvantages associated with the CI&#46; Jaruratanasirikul et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> point out that EI would achieve the PK-PD objective of 40&#37; <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>MIC with a likelihood of 90&#37; compared to 79&#37; with II for doses of 0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; 1<span class="elsevierStyleHsp" style=""></span>g&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; and 2<span class="elsevierStyleHsp" style=""></span>g&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">To ensure that patients receive sufficient meropenem to achieve cure while avoiding exposure to toxic degradation products&#44; chemical stability and physical compatibility of meropenem should be maintained throughout the period of administration&#46; Stability data available until now indicate that meropenem in 0&#46;9&#37; sodium chloride &#40;NS&#41; at concentrations ranged from 4 to 20<span class="elsevierStyleHsp" style=""></span>mg&#47;mL is stable for 3&#8211;7 days at 5<span class="elsevierStyleHsp" style=""></span>&#176;C in elastomeric infusion devices for CI<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;13</span></a> and that meropenem 1 or 2<span class="elsevierStyleHsp" style=""></span>g in 100<span class="elsevierStyleHsp" style=""></span>mL with NS &#40;10 and 20<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#44; respectively&#41; is stable for 5 days at 5<span class="elsevierStyleHsp" style=""></span>&#176;C and 10<span class="elsevierStyleHsp" style=""></span>h at 25<span class="elsevierStyleHsp" style=""></span>&#176;C in infusion bags for EI&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#8211;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The objective of the present study is to determine the chemical stability and physical compatibility of meropenem in elastomeric infusion devices and infusion bags at concentrations used in clinical practice &#40;25 and 120<span class="elsevierStyleHsp" style=""></span>mg&#47;mL in infusors&#59; 4 and 8<span class="elsevierStyleHsp" style=""></span>mg&#47;mL in infusion bags&#41; at different temperatures &#40;4&#46;5&#44; 24&#46;5 or 32<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#44; in order to evaluate the stability of the preparation during its administration by CI or EI and the possibility of anticipated preparation of admixtures&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Reagents and materials</span><p id="par0030" class="elsevierStylePara elsevierViewall">As reagents&#44; meropenem 1000<span class="elsevierStyleHsp" style=""></span>mg powder for injection &#40;Aurovitas Spain&#44; Barcelona&#44; Spain&#41;&#44; NS in Viaflo&#174; infusion bag &#40;made of polyethylene&#44; polyamide and polypropilen&#41; of 50 or 250<span class="elsevierStyleHsp" style=""></span>mL &#40;Baxter&#44; Barcelona&#44; Spain&#41;&#44; sterile water &#40;API&#41; for injection &#40;B&#46; Braun&#44; Barcelona&#44; Spain&#41;&#44; acetonitrile &#40;Scharlab&#44; Barcelona&#44; Spain&#41; and sodium dihydrogen phosphate &#40;NaH<span class="elsevierStyleInf">2</span>PO<span class="elsevierStyleInf">4</span>&#59; Panreac&#44; Barcelona&#44; Spain&#41; were adquired&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Singleday&#174; 2<span class="elsevierStyleHsp" style=""></span>mL&#47;h 50<span class="elsevierStyleHsp" style=""></span>mL and Folfusor&#174; LV 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL &#40;Baxter&#44; Barcelona&#44; Spain&#41; elastomeric infusion devices &#40;made of polyisoprene&#41; and light protection bags &#40;Diffuplast&#44; Italy&#41; were used&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Admixtures</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A</span>dmixtures were prepared by duplicate following Good Manufacturing Practice &#40;GMP&#41;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#44; being 24 the total number of admixtures&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows dose&#44; volume and container of the admixtures&#46; To prepare them&#44; meropenem powder was reconstituted with API and dilluted to the corresponding volume with NS&#46; All admixtures were introduced in ligh protection bags&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Stability studies</span><p id="par0045" class="elsevierStylePara elsevierViewall">Chemical stability and physical compatibility of meropenem were evaluated at different concentrations and temperatures &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Admixtures in infusors were stored at 32<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; since it is the physiological temperature reached by the infusor during its administration&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> and at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C because previous studies indicate that meropenem is more stable under refrigeration than at high temperatures&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Admixtures in infusion bags were also stored at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C and at 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; as room temperature during administration&#46; The possibility of anticipated preparation was evaluated by storing admixtures at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C followed by 32<span class="elsevierStyleHsp" style=""></span>&#176;C for infusors or 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C for infusion bags&#59; time of refrigeration was greater in admixtures in infusors &#40;12<span class="elsevierStyleHsp" style=""></span>h&#41; than in infusion bags &#40;6<span class="elsevierStyleHsp" style=""></span>h&#41; since its preparation is more complex&#44; takes more time and due to the high workload of nursing staff&#44; it can be prepared during a 12-h shift&#46; Time of study was 5&#8211;6 days for infusors and 1 day for infusion bags&#59; the fact of evaluating chemical stability and physical compatibility for more than 1 day in infusors is that its cost is highest and the preparation is most complex so&#44; in case of not administering the infuser to the patient&#44; it can be reused&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Chemical stability of meropenem in each admixture was determined by measuring its concentration by high performance liquid chromatography &#40;HPLC&#41; in an aliquot of 1<span class="elsevierStyleHsp" style=""></span>mL extracted at different sampling times&#58; just after preparation &#40;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0<span class="elsevierStyleHsp" style=""></span>h&#41; and at 2&#44; 4&#44; 8&#44; 12 and 24<span class="elsevierStyleHsp" style=""></span>h and then every 24<span class="elsevierStyleHsp" style=""></span>h for 5&#8211;6 days for admixtures stored in infusors and at 2&#44; 4&#44; 6&#44; 9&#44; 12&#44; 14 and 24<span class="elsevierStyleHsp" style=""></span>h for admixtures in infusion bags&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">An Agilent Technologies 1100 HPLC system &#40;Agilent Technologies Inc&#46;&#44; Waldbronn&#44; Karlsruhe&#44; Germany&#41; with a diode array detector was used for the analysis&#46; The HPLC method was modified from Foy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Chromatographic separations were achieved on a reversed phase column C18&#174; &#40;150<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>4&#46;6<span class="elsevierStyleHsp" style=""></span>mm inner diameter&#59; 5<span class="elsevierStyleHsp" style=""></span>&#956;m&#41; with a gradient of mobile phase containing 0&#46;01<span class="elsevierStyleHsp" style=""></span>M NaH<span class="elsevierStyleInf">2</span>PO<span class="elsevierStyleInf">4</span> pH 2 and acetonitrile &#40;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0<span class="elsevierStyleHsp" style=""></span>min&#44; 93&#58;7&#44; v&#47;v&#59; <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>min&#44; 88&#58;12&#44; v&#47;v&#59; <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>min&#44; 51&#58;49&#44; v&#47;v&#44; respectively&#41; at a flow rate of 0&#46;8<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46; Column temperature was 25<span class="elsevierStyleHsp" style=""></span>&#176;C and injection volume&#44; 5<span class="elsevierStyleHsp" style=""></span>&#956;L&#59; wavelength was 298<span class="elsevierStyleHsp" style=""></span>nm and time of analysis&#44; 17<span class="elsevierStyleHsp" style=""></span>min&#46; Chromatographic method was previously validated according to the International Conference on Harmonization &#40;ICH&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> and was adequate to determine meropenem in admixtures&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The remaining concentration of meropenem &#40;&#37;RC&#41; at each sampling time was expressed as the mean percentage and standard deviation &#40;SD&#41; of the initial concentration &#40;after preparation&#41;&#59; the initial concentration was expressed as 100&#37;&#46; The stability of a solution for infusion is maintained when the &#37;RC remains &#62;90&#37; throughout the infusion period&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#44;20</span></a> So&#44; the parameter used to define chemical stability was <span class="elsevierStyleItalic">T</span>90&#44; time at which &#37;RC was 90&#37;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The pair data concentration-time were adjusted&#44; if possible&#44; to a zero- &#40;Eq&#46; <a class="elsevierStyleCrossRef" href="#eq0005">&#40;1&#41;</a>&#41; or first-order kinetic equation &#40;Eq&#46; <a class="elsevierStyleCrossRef" href="#eq0010">&#40;2&#41;</a>&#41;&#46; <span class="elsevierStyleItalic">T</span>90 was estimated by considering the time at which the 95&#37; one-sided confidence limit for the mean curve intersects 90&#37; of the initial concentration of meropenem&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia><elsevierMultimedia ident="eq0010"></elsevierMultimedia>being <span class="elsevierStyleItalic">C</span>&#44; meropenem concentration at a specific sampling time&#59; <span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">0</span>&#44; meropenem concentration at <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#59; <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">0</span>&#44; zero-order degradation rate constant and <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">1</span>&#44; first-order degradation rate constant&#59; <span class="elsevierStyleItalic">t</span>&#44; sampling time&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Physical compatibility of each admixture was evaluated at each sampling time by measuring&#44; in an extracted aliquot of 5<span class="elsevierStyleHsp" style=""></span>mL&#58; &#40;i&#41; pH&#44; with glass electrode and pH-meter &#40;model 3510&#44; Jenway&#44; UK&#41;&#59; incompatibility if variation of pH is &#62;5&#37;&#59; &#40;ii&#41; color changes&#44; cloudiness &#40;turbidity&#41; and&#47;or precipitation&#44; measured by visual inspection&#59; incompatibility if some of these parameters appear&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows chemical stability and physical compatibility parameters for all the admixtures&#58; &#40;a&#41; the average of &#37;RC at the end of the study and the parameter <span class="elsevierStyleItalic">T</span>90&#59; &#40;b&#41; the initial value of pH&#44; time at which variation of pH was &#62;5&#37; and time at which the color of admixture changed&#59; &#40;c&#41; expiration time&#44; by considering chemical stability and physical compatibility&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">As regards admixtures in infusors &#40;admixtures 1&#8211;12&#41;&#44; the increase in temperature from 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C to 32<span class="elsevierStyleHsp" style=""></span>&#176;C lead to a 64&#37; decrease in &#37;RC at the end of the study and significant decreases in <span class="elsevierStyleItalic">T</span>90 from 5 days to 14<span class="elsevierStyleHsp" style=""></span>h in Singleday&#174; 2<span class="elsevierStyleHsp" style=""></span>mL&#47;h 50<span class="elsevierStyleHsp" style=""></span>mL &#40;120<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41; and from 4 days to 7<span class="elsevierStyleHsp" style=""></span>h in Folfusor&#174; LV 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41;&#46; Similar &#37;RC and <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">90</span> values were obtained for admixtures stored at 32<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; with and without pre-cooling&#46; In admixtures with a concentration of meropenem of 120<span class="elsevierStyleHsp" style=""></span>mg&#47;mL &#40;admixtures 1&#8211;4&#41;&#44; there were variations of pH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5&#37; from day 5<span class="elsevierStyleHsp" style=""></span>at 4&#46;5 and 32<span class="elsevierStyleHsp" style=""></span>&#176;C and visual color changes were observed earliest that in admixtures with low meropenem concentration &#40;admixtures 7&#8211;12&#41;&#46; So&#44; expiration time was shorter when increasing the concentration of meropenem&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In admixtures stored in Viaflo&#174; &#40;admixtures 13&#8211;24&#41;&#44; &#37;RC was &#8805;90&#37; at the end of the study &#40;1 day&#41;&#46; Variations of pH were &#60;5&#37; in all cases and visual color changes were not observed&#46; So&#44; expiration time was at least 1 day&#44; since it is the time of the study&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the kinetic parameters for meropenem degradation and estimated <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">90</span> values&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Previous studies indicate that the stability of meropenem depends on the diluent&#44; concentration&#44; temperature and pH&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;21</span></a> NS is usually used as diluent since it improves stability of meropenem compared to other diluents such as glucose 5&#37; or 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Stability of meropenem in NS solution decreases with increasing concentration of meropenem<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;21</span></a> and with increasing temperatures&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;17&#44;21</span></a> being stable for a longer time under refrigeration and degrading more quickly at temperatures upper than 35<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;21&#44;22</span></a> In our study&#44; there were not statistically significant differences in &#37;RC and <span class="elsevierStyleItalic">T</span>90 between admixtures in infusors with different meropenem concentration &#40;admixtures 1&#8211;6&#44; 120<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#59; admixtures 7&#8211;12&#44; 25<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41; but physical compatibility and consequently&#44; expiration time were reduced at high meropenem concentration and at high temperature &#40;32<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; The observed color changes could be a consequence of the degradation of meropenem by hydrolysis of the beta-lactam ring&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> favored by high concentration and temperature&#59; when color changes&#44; it is recommended not to administer admixtures since physical incompatibility is usually related to loss of potency and increase in toxicity&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">So&#44; the only admixture that can be administered in CI of 24<span class="elsevierStyleHsp" style=""></span>h is meropenem 6<span class="elsevierStyleHsp" style=""></span>g in 240<span class="elsevierStyleHsp" style=""></span>mL of NS in Folfusor&#174; LV 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL as long as it is infused at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; being expiration time of 4 days&#46; This admixture becomes a possible alternative in Home Care Units&#44; where EI &#40;administration every 8<span class="elsevierStyleHsp" style=""></span>h and drug withdrawal after 3&#8211;4<span class="elsevierStyleHsp" style=""></span>h&#41; is not a viable option&#46; Several studies have proposed different ways to maintain infusors under refrigeration during its administration such as placing the infusors with frozen ice-bricks in a standard carry-bag<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;21</span></a> or in a cassette attached to an infusion pump<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#59; Grant et al&#46; indicate that it is possible to maintain elastomeric infusion devices at 2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C over 24<span class="elsevierStyleHsp" style=""></span>h in a cassette between two ice-bricks&#44; which are changed every 8<span class="elsevierStyleHsp" style=""></span>h&#44; at a room temperature of 20&#8211;25<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Admixtures containing 1 or 2<span class="elsevierStyleHsp" style=""></span>g of meropenem in 250<span class="elsevierStyleHsp" style=""></span>mL of NS in Viaflo&#174; can be used for II &#40;15&#8211;30<span class="elsevierStyleHsp" style=""></span>min&#41; or EI &#40;3&#8211;4<span class="elsevierStyleHsp" style=""></span>h&#41; at 4&#46;5 or 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows <span class="elsevierStyleItalic">T</span>90 of admixtures of 1 or 2<span class="elsevierStyleHsp" style=""></span>g of meropenem in 100<span class="elsevierStyleHsp" style=""></span>mL and 250<span class="elsevierStyleHsp" style=""></span>mL of NS at room temperature or under refrigeration&#46; As can be observed&#44; increasing the final volume from 100 to 250<span class="elsevierStyleHsp" style=""></span>mL&#44; chemical stability increases up to 1 day at 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; which would allow EI of meropenem 1 or 2<span class="elsevierStyleHsp" style=""></span>g in 3&#8211;4<span class="elsevierStyleHsp" style=""></span>h&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Consequently&#44; as previous studies have shown in clinical practice&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24&#8211;26</span></a> the fact of administering meropenem by CI or EI would increase the clinical cure rate by 30&#37; compared to conventional administration of beta-lactams in critical or septic patients&#46; These results are also supported by meta-analysis in critically ill patients or with infections caused by high MIC pathogens&#44; which indicate higher clinical cure rate and lower mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#8211;30</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Finally&#44; the possibility of preparation in advance of admixtures of meropenem in NS in infusors and infusion bags was evaluated&#46; The results obtained in this study indicated that preparation in advance is not possible in infusors for CI since after 12<span class="elsevierStyleHsp" style=""></span>h stored at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">90</span> was 5<span class="elsevierStyleHsp" style=""></span>h at 32<span class="elsevierStyleHsp" style=""></span>&#176;C in Singleday&#174; 2<span class="elsevierStyleHsp" style=""></span>mL&#47;h 50<span class="elsevierStyleHsp" style=""></span>mL and 2<span class="elsevierStyleHsp" style=""></span>h in Folfusor&#174; LV 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL&#44; being the time of administration to patients of 24<span class="elsevierStyleHsp" style=""></span>h&#46; Nevertheless&#44; preparation in advance is viable in Viaflo&#174; if storing the admixture 6<span class="elsevierStyleHsp" style=""></span>h at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C and administering during the following 18<span class="elsevierStyleHsp" style=""></span>h at 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; enough time not only for II &#40;15&#8211;30<span class="elsevierStyleHsp" style=""></span>min&#41; but also for EI &#40;3&#8211;4<span class="elsevierStyleHsp" style=""></span>h&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; the administration of meropenem 6<span class="elsevierStyleHsp" style=""></span>g in perfusion of 24<span class="elsevierStyleHsp" style=""></span>h in 240<span class="elsevierStyleHsp" style=""></span>mL of 0&#46;9&#37; NaCl in infusor Folfusor&#174; LV 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL could be possible if the admixture is infused at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; This study also increases chemical stability and physical compatibility of meropenem 1 or 2<span class="elsevierStyleHsp" style=""></span>g in 0&#46;9&#37; NaCl in Viaflo&#174; infusion bag &#40;250<span class="elsevierStyleHsp" style=""></span>mL&#41; to 24<span class="elsevierStyleHsp" style=""></span>h&#44; being between 3 and 10<span class="elsevierStyleHsp" style=""></span>h<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;14</span></a> in 100<span class="elsevierStyleHsp" style=""></span>mL&#59; therefore&#44; extended infusion in 3&#8211;4<span class="elsevierStyleHsp" style=""></span>h is also feasible&#44; allowing its use in septic or critically patients or with high MIC Gram negative bacteria in which a higher clinical cure rate has been evidenced&#46; Moreover&#44; anticipated preparation of admixtures of meropenem in Viaflo&#174; is possible&#44; as opposed to its usual method of preparation at the time of administration because of its short stability&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">As a limitation on this study&#44; the results of chemical stability and physical compatibility of meropenem obtained are applicable to infusion bags made of polyethylene&#44; polyamide and polypropilen &#40;Viaflo&#174;&#41; and infusors of polyisoprene &#40;Singleday&#174; and Folfusor&#174;&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">Authors state no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prolonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients&#46; This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Admixtures in study were&#58; &#40;i&#41; meropenem 6<span class="elsevierStyleHsp" style=""></span>g in 0&#46;9&#37; sodium chloride &#40;NS&#41; in infusor of 2<span class="elsevierStyleHsp" style=""></span>mL&#47;h 50<span class="elsevierStyleHsp" style=""></span>mL or 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h 240<span class="elsevierStyleHsp" style=""></span>mL&#59; &#40;ii&#41; meropenem 1 or 2<span class="elsevierStyleHsp" style=""></span>g in NS in infusion bag of 250<span class="elsevierStyleHsp" style=""></span>mL&#46; Temperatures of study were&#58; &#40;i&#41; infusor&#58; 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 32<span class="elsevierStyleHsp" style=""></span>&#176;C or 12<span class="elsevierStyleHsp" style=""></span>h at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C followed by 32<span class="elsevierStyleHsp" style=""></span>&#176;C&#59; &#40;ii&#41; Infusion bag&#58; 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C or 6<span class="elsevierStyleHsp" style=""></span>h at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C followed by 24&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Time of study was 5&#8211;6 days in infusor and 1 day in infusion bag&#46; Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Chemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature&#46; Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Administration of meropenem 6<span class="elsevierStyleHsp" style=""></span>g in infusion of 24<span class="elsevierStyleHsp" style=""></span>h in 240<span class="elsevierStyleHsp" style=""></span>mL of 0&#46;9&#37; NaCl in infusor of 10<span class="elsevierStyleHsp" style=""></span>mL&#47;h could be possible if the admixture is infused at 4&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Extended infusion of meropenem 1 or 2<span class="elsevierStyleHsp" style=""></span>g in 0&#46;9&#37; NaCl in infusion bag &#40;250<span class="elsevierStyleHsp" style=""></span>mL&#41; in 3&#8211;4<span class="elsevierStyleHsp" style=""></span>h is also feasible&#46; Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24<span class="elsevierStyleHsp" style=""></span>h&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La infusi&#243;n intravenosa prolongada de beta-lact&#225;micos aumenta la velocidad de curaci&#243;n cl&#237;nica comparada con la administraci&#243;n convencional en pacientes cr&#237;ticos o s&#233;pticos&#46; Este estudio tiene como objetivo determinar la estabilidad qu&#237;mica y la compatibilidad f&#237;sica de meropenem en condiciones utilizadas en la pr&#225;ctica cl&#237;nica para evaluar la estabilidad de la preparaci&#243;n durante su administraci&#243;n y la posibilidad de la preparaci&#243;n anticipada&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Las mezclas en estudio fueron&#58; &#40;I&#41; meropenem 6g en cloruro s&#243;dico 0&#44;9&#37; &#40;SN&#41; en infusor de 2mL&#47;h 50 mL o 10mL&#47;h 240mL&#59; &#40;iii&#41; meropenem 1 o 2g en SN en bolsa de infusi&#243;n de 250mL&#46; Las temperaturas de estudio fueron&#58; &#40;i&#41; infusor&#58; 4&#44;5&#176;C&#44; 32&#176;C o 12h a 4&#44;5&#176;c seguido de 32&#176;C&#59; &#40;ii&#41; bolsa de infusi&#243;n&#58; 4&#44;5&#176;C&#44; 24&#44;5&#176;C o 6h a 4&#44;5&#176;c seguido de 24&#44;5&#176;C&#46; El tiempo de estudio fue de 5-6 d&#237;as en infusor y 1 d&#237;a en bolsa de infusi&#243;n&#46; Se evalu&#243; la estabilidad qu&#237;mica mediante cromatograf&#237;a l&#237;quida de alta resoluci&#243;n y la compatibilidad f&#237;sica por medida de pH e inspecci&#243;n visual&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La estabilidad qu&#237;mica y la compatibilidad f&#237;sica de meropenem en las mezclas en infusores disminuyeron al aumentar la concentraci&#243;n de meropenem y la temperatura&#46; Las mezclas en bolsas de infusi&#243;n mostraron estabilidad qu&#237;mica y compatibilidad f&#237;sica durante al menos 1 d&#237;a&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n de meropenem 6g en infusi&#243;n de 24h en 240 mL de cloruro s&#243;dico 0&#44;9&#37; en infusor de 10ml&#47;h podr&#237;a ser posible si la mezcla es administrada a 4&#44;5&#176;C&#46; La infusi&#243;n extendida de 1 o 2g en cloruro s&#243;dico 0&#44;9&#37; en bolsa de infusi&#243;n &#40;250 mL&#41; en 3-4h es tambi&#233;n viable&#46; Puede realizarse la preparaci&#243;n anticipada de mezclas de meropenem en bolsas de infusi&#243;n con una estabilidad de 1 d&#237;a&#46;</p></span>"
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">240&nbsp;\t\t\t\t\t\t\n
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