Introduction: The purpose of our study was to evaluate the safety, tolerability, and pharmacokinetics of furaprevir, a new highly selective hepatitis C virus NS3/4A protease inhibitor. Methods: The study was divided into 2 parts: part A (single ascending dose study [SAD]) and part B (multiple ascending dose study [MAD]). A total of 62 healthy subjects were enrolled in the studies. DNA samples were extracted from all subjects, and genotypes of CYP3A5*3, CYP3A4*1 G, and POR*28 were analyzed by ligase detection reaction. Results: We used nonlinear mixed-effects model (NONMEM) to construct furaprevir population pharmacokinetics model. (1) In SAD, Cmax and area under the curve (AUC) were greater than dose increased ratio in the dose rang of 100–400 mg; (2) In MAD, Cmax and AUC increased in an approximately dose-proportional manner in the dose range of 200–600 mg; (3) A one-compartment model with transit absorption described the plasma concentrations of furaprevir. The apparent clearance was estimated at 33.4 L/h. The distribution volume of compartment (V2) was 219.0 L. No serious adverse event occurred in the studies. But other screening gene mutations had no statistically significant effects on the pharmacokinetics of furaprevir. Conclusion: Food significantly impacts the bioavailability of furaprevir. Furaprevir does not accumulate in vivo after multiple rising doses and has demonstrated safety and tolerability in healthy subjects, supporting its further investigation in patients with hepatitis C.

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