Atazanavir
Atazanavir. HIV protease inhibitor — competitive inhibition of HIV-1 aspartyl protease blocks gag/gag-pol polyprotein cleavage and prevents… Oral half-life 9.9 h.
HIV protease inhibitor — competitive inhibition of HIV-1 aspartyl protease blocks gag/gag-pol polyprotein cleavage and prevents production of mature virions. Almost always coadministered with a CYP3A4 booster (cobicistat or ritonavir) for adequate exposure. Distinctive among PIs for its inhibition of UGT1A1 — causes asymptomatic Gilbert-like unconjugated hyperbilirubinemia in most users (visible as scleral icterus at high exposure); not hepatotoxic, doesn't require discontinuation. Requires acid for absorption — clinically significant interaction with PPIs / H2 blockers / antacids. Otherwise generally well tolerated long-term. PK (Reyataz label, boosted 300/100 mg PO qd with RTV at SS): Cmax 6129 ng/mL, AUC(0-24) 57039 ng·h/mL, Tmax ~2.5 h, t½ 9-18 h boosted (7-8 h unboosted). Light meal ↑ AUC ~33% + Cmax ~40% (food taken with dose). CL/F ≈ 5.3 L/h, V/F ≈ 91 L.
PK: A PUBLISHED ONE-COMPARTMENT MODEL EXISTS WITH EXACTLY THIS SOLVER STRUCTURE AND WAS NOT USED — "Final estimates of apparent oral clearance (CL/F), volume of distribution (V/F) and absorption rate constant ... were 7.7 L/h (5, 29), 103 L (13, 48) and 3.4 h(-1) (34, 154); a lag-time of 0.96 h (1)". The stored absorption rate was 5.7x too slow and the volume 12% low. THE HALF-LIFE WAS REFUTED BY THE RECORD OWN REFERENCE: "Geometric mean terminal elimination half-life to 72 h of atazanavir was 8.35 h and not different from the 0-24 h half-life (9.91 h)", on the same boosted regimen, where the source_label claimed 9-18 h and that range could not be verified anywhere. CLASS 6 IS ACQUITTED DELIBERATELY: there is no human intravenous atazanavir, so every published volume is apparent and pinning F to 1 is the correct convention rather than a gap. MY OWN PRIOR THAT THE BOOSTED AND UNBOOSTED STATES DIFFER SEVERAL-FOLD IS REFUTED — "Atazanavir CL/F was reduced by ritonavir by 45%", about 1.8x — but the record still spans two clinical states, because its dose block reaches 400 mg, WHICH IS THE UNBOOSTED REGIMEN, while every stored parameter describes the boosted one. The lag time is not representable here, so absorption starts about an hour early.
Pharmacokinetics
- Oral — t½ 9.9 h · F 100% · ka 3.4 h⁻¹ · Vd 103 L
Sources: PMID:19043924, PMID:19329800