[Pharmacology, pharmacokinetic features and interactions of atazanavir].
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.
López-Cortés
Luis F
LF
Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla, España. lflopez@telefonica.net
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D001682:Biological Availability; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000099148:UGT1A1 Enzyme
D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D001798:Blood Proteins; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D014453:Glucuronosyltransferase; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000099148:UGT1A1 Enzyme; C510163:CYP3A4 protein, human