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Atazanavir (ATV) es un inhibidor de la proteasa (IP) del virus de la inmunodeficiencia humana (VIH) con alta actividad in vitro frente al VIH-1, que muestra una actividad aditiva en presencia de otros antirretrovirales y una actividad sinérgica con otros IP. Su absorción por vía oral es superior al 68%, alcanzándose la concentración máxima (Cmáx) aproximadamente 2-3 h después de su administración. Su absorción está relacionada con el pH gástrico, recomendándose su administración tras las comidas. La farmacocinética de ATV no es lineal; es decir, sus concentraciones plasmáticas (Cp) no aumentan en proporción con las dosis. ATV se une aproximadamente en un 86% a las proteínas plasmáticas. Su penetración en el líquido cefalorraquídeo, el semen o las secreciones genitales es variable, pero en general inferior al 10-20%. Su paso a través de la placenta, medido como la media de los cocientes entre las Cp en sangre de cordón umbilical respecto a las maternas, es de 0,13. El ATV es metabolizado mediante oxidación por las enzimas del citocromo P450, eliminándose con posterioridad por vía biliar en forma libre o glucuronidada (80%) y por la orina. Asimismo, es un inhibidor competitivo débil de la CYP3A4 y un fuerte inhibidor de la uridina difosfatoglucuronosiltransferasa 1A1, que es la causa de la frecuente hiperbilirrubinemia tras su administración y de sus interacciones farmacológicas.
Palabras clave:
Atazanavir
Farmacología
Farmacocinética
Atazanavir (ATV) is an HIV protease inhibitor (IP) with a high in vitro activity against HIV-1, that demonstrates a high additive activity in the presence of other antiretrovirals and a synergic activity with other PI. Oral absorption is greater than 68%, maximum concentration (Cmax) being reached approximately 2 to 3 h after its administration. Its absorption is dependent on gastric pH, its administration being recommended after meals. The pharmacokinetics (PK) of ATV are non-linear; that is to say, its plasma concentrations (Cp) do not increase in proportion to the dose. ATV is approximately 86% bound to plasma proteins. Its entry into the cerebrospinal fluid, semen or genital secretions varies but is generally less than 10-20%. Its passage across the placenta, measured as the mean of the ratios between the Cp in umbilical cord and maternal blood, is 0.13. ATV is metabolised by oxidation by cytochrome P450 enzymes, subsequently being eliminated by the bile duct in the free or glucuronide form (80%) and by the urine. ATV is a weak competitive inhibitor of CYP3A4 and a strong inhibitor of uridine diphosphate-glucuronosyltransferase 1A1, which is the cause of the frequent high plasma bilirubin after its administration and of its pharmacological interactions.
Key words:
Atazanavir
Pharmacology
Pharmacokinetics
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