Methadone dosing in patients on ritonavir-boosted-based highly active antiretroviral therapy

Lozano, Roberto; Domeque, Nieves; Frutos, Alberto Jose

doi:10.1016/j.medcle.2018.03.040

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e.g. combinations of RTV with atazanavir, lopinavir or darunavir) and extensively metabolized by cytochrome P450 (CYP) 3A4 for which is a potent inhibitor.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> Also, we know that MTD is mainly metabolized by CYP 3A4 and CYP 2B6 to which it potently induces.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Therefore, the sharing of the CYP 3A4 metabolic pathway, results in a metabolism-based DDI, between MTD and RTV.Despite being a well-known DDI, the mechanism by which RTV alters the clearance of MTD remains controversial, so is its influence on plasma MTD levels. Which finally manifests in form of great variability in the dosage of MTD, when used in conjunction with RTV: from not modifying the dose of MTD until increases up to 40%.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Thus, we aimed to analyze the influence of ritonavir-based HAART on MTD-dose of patients included in MMT programs, in order to avoid the variability of its dosage.For this, a retrospective observational clinical study was conducted. The initial sample was composed of HIV(+)-patients treated with HAART and included in our MMT program, during a 10-years follow-up period (n=130). Since it was not an experimental work no ethic committee review was required. However, it did need to meet the ethical standards of the Declaration of Helsinki.Firstly, we collected data of clinically relevant metabolism-based drug-drug interactions (DDI) between ARVs and MTD. The results showed that 26% of patients display ARVs–MTD interactions, of which the MTD–RTV interaction (23%) was the most prevalent. Secondly, after excluding patients (n=15) who had MTD interactions with drugs other than RTV we obtained the study final sample (n=115).From this final sample, we compared the mean value of the MTD-dose, adjusted by body weight, of HIV(+)-patients on RTV-based HAART (RTV-group; RTV dose of 100–200mg/day; n=35) vs. of HIV(+)-patients on HAART that excluded RTV (non-RTV-group; n=80). As result, we found that average MTD-dose in the RTV-group was 50% higher than non-RTV-group (1.2±0.5mg/kg vs 0.8±0.5mg/kg, 95% CI=0.199 to 0.601, p<.0001), <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>These data coincide with those of the authors who reported a significant decrease in plasma MTD values (up to 40%),<a class="elsevierStyleCrossRef" href="#bib0045">4</a> when used in conjunction with RTV; also, support the observations of Kharasch et al.,<a class="elsevierStyleCrossRef" href="#bib0050">5</a> that CYP3A does not mediate the interaction between MTD and RTV. In addition, the results suggest that RTV would first inhibit CYP3A4, increasing plasma MTD levels and, this increase, in turn, would secondarily cause an increase in the self-induction of CYP2B6. Thus, the MTD-inhibition of CYP3A4 together with the self-induction of CYP2B6, would result in an overall decrease of plasma MTD levels; which, ultimately, could lead to opiate withdrawal symptoms (for example, fatigue, anxiety, restlessness), and cause patients to require higher doses of MTD.In conclusion, up to date, MTD-RTV continues to be the most prevalent DDI among HIV(+)-patients receiving HAART and included in MMT programs. These patients, due to the decrease of the values of MTD in plasma when administered in conjunction with RTV-boosted-based HAART (100–200mg/day), need to increase their dose of MTD (mg/kg-body weight) by 50%.Finally, it should be noted, as the most important limitation of this DDI analysis and due to the size of the sample and the absence of data, that it could not evaluate the influence of other factors, such as sex, age, the different combination of ARVs, and concomitant treatments for other infectious and psychiatric co-morbidities." "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 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" => "ABV: abacavir; ARV: antiretroviral; ATV: atazanavir; DRV: darunavir; EFV: efavirenz; FTC: emtricitabine; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; LPV: lopinavir; MTD: methadone; NVP: nevirapine; RTV: ritonavir; RTG: raltegravir; 3TC: lamivudine; TDF: tenofovir; BMI: Body Mass Index." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">RTV-group (N=35) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Non-RTV-group (N=80) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Patients characteristics, mean (SD)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female, No. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 (8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight, kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI, kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MTD-dose/weight, mg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">HAART (ARVs combinations; between brackets, [RTV-boosted ARVs]), N(%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EFV-FTV-TDF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 (64) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FTC-TDF-NVP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FTC-TDF-RTG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (4.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3TC-ABV-EFV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-ART \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (14.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FTC-TDF-[DRV-RTV] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (48.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FTC-TDF-[ATZ-RTV] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FTC-TDF-[LPV-RTV] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3TC-ABV-[LPV-RTV] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (8.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3TC-ABV-[ATV-RTV] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1959485.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patients characteristics and antirretroviral drug regimens." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacological maintenance treatments of opiate addiction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Bell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bcp.12051" "Revista" => array:6 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "2014" "volumen" => "77" "paginaInicial" => "253" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23210630" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multidose pharmacokinetics of ritonavir and zidovudine in human immunodeficiency virus-infected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Cato" 1 => "J. Qian" 2 => "A. Hsu" 3 => "B. Levy" 4 => "J. Leonard" 5 => "R. Granneman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "1998" "volumen" => "2" "paginaInicial" => "1788" "paginaFinal" => "1793" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanism of autoinduction of methadone N-demethylation in human hepatocytes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.D. Campbell" 1 => "A. Crafford" 2 => "B.L. Williamson" 3 => "E.D. Kharasch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1213/ANE.0b013e3182918252" "Revista" => array:6 [ "tituloSerie" => "Anesth Analg" "fecha" => "2013" "volumen" => "117" "paginaInicial" => "52" "paginaFinal" => "60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23733841" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased methadone effect after ritonavir initiation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.M. Geletko" 1 => "A.D. Erickson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "2000" "volumen" => "20" "paginaInicial" => "93" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10641980" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytochrome P4503A does not mediate the interaction between methadone and ritonavir–lopinavir" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.D. Kharasch" 1 => "K. 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ISSN: 2387-0206

Launched in 1943, Medicina Clínica is a fortnightly journal aimed at the promotion of clinical research and practice among internal medicine and other specialists. The key characteristics of Medicina Clínica are the scientific and methodological rigor of its manuscripts, the topicality of its contents, and, especially, its practical focus with highly useful information for clinical practice. Medicina Clínica is predominantly interested in publishing original research manuscripts, which are rigorously selected according to their quality, originality, and interest, and also in continued medical education-oriented manuscripts, which are commissioned by the journal to relevant authors (Editorials, Reviews, and Diagnosis and Treatment). These manuscripts contain updated topics with a major clinical or conceptual relevance in modern medicine. The journal adheres to the standards of academic research publications in all aspects including peer-review and ethical principles. Medicina Clínica is included in the General and Internal Medicine category of Thomson Reuters.

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Impact factor

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years.

© Clarivate Analytics, Journal Citation Reports 2022

Impact factor 2023

2.6

Citescore

CiteScore measures average citations received per document published.

Citescore 2023

3.1

SJR

SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.

SJR 2023

0.371

SNIP

SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.

SNIP 2023

0.511

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Vol. 152. Issue 4.

Pages 161-162 (February 2019)

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