Single‐Dose and Multiple‐Dose Pharmacokinetics of Vaniprevir in Healthy Men

Abstract

Vaniprevir is an inhibitor of the hepatitis C virus (HCV) NS3/4A protease. The aim of these double-blind, placebo-controlled phase I studies was to evaluate the safety and pharmacokinetics of vaniprevir in healthy male volunteers. The primary objective for both studies was the safety and tolerability of vaniprevir. Single-dose and steady-state pharmacokinetics were also assessed. In both studies, there was no apparent relationship between the frequency or intensity of adverse events and vaniprevir dose. At single doses >20 mg, the plasma area under the curve (AUC) 0-Ý and maximum concentration (C max ) increased in a greater-thandose-proportional manner. The geometric mean ratios (GMRs; fed/fasted) were 1.22 and 0.79 for AUC 0-Ý and C max , respectively. Following multiple doses, GMR accumulations for AUC 0-12h and C max (day 14/day 1) ranged from 1.53 to 1.90 and from 1.41 to 1.92, respectively. These data support the use of vaniprevir with peginterferon and ribavirin in patients with HCV infection.