Grazoprevir
Grazoprevir. HCV NS3/4A protease inhibitor — Zepatier component (with elbasvir). Mild OATP1B1/B3 inhibitor → caution with statins. CYP3A4… Oral half-life 31 h.
HCV NS3/4A protease inhibitor — Zepatier component (with elbasvir). Mild OATP1B1/B3 inhibitor → caution with statins. CYP3A4 substrate. Contraindicated in moderate/severe hepatic impairment. PK (Zepatier label, 100 mg PO qd SS): Cmax 165 ng/mL, AUC 1420 ng·h/mL, Tmax 2 h (range 30 min-3 h), t½ 31 h, F 27%. High-fat meal increases grazoprevir AUC 1.5-fold + Cmax 2.8-fold — a substantial food effect. Mild OATP1B1/B3 inhibitor — caution with statins.
PK: THE ABSORPTION RATE PREDICTED A PEAK AT 5.08 h AGAINST ITS OWN LABEL STRING MEDIAN OF 2 h. As with its co-formulated partner, every other stored figure verifies verbatim against the Zepatier label, including the food effect quoted in the mechanism prose. The stored volume was likewise back-solved and reproduces the label exposure to 0.8%, where the label published apparent volume of 1250 L would overshoot by 50%; it is deliberately left alone. A LIMIT IS RECORDED AS IRREDUCIBLE RATHER THAN CHASED: this record under-predicts the label peak concentration by 2.3x and NO CHOICE OF ABSORPTION RATE CAN FIX IT — with exposure and half-life both pinned to verbatim label values, the dose-over-volume ceiling is far below the observed peak. Grazoprevir is strongly biexponential because of active hepatic uptake, and that is a limitation of one compartment rather than a defect in the data.
Pharmacokinetics
- Oral — t½ 31 h · F 27% · ka 2.35 h⁻¹ · Vd 844 L
Sources: PMID:32104104