[Pharmacology, pharmacokinetic features and interactions of atazanavir]

Abstract

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 (C(max)) 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 (C(p)) 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 C(p) 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.