Pharmacokinetic characteristics of telaprevir in healthy Korean male subjects and comparisons with Japanese

Abstract

Introduction

Telaprevir, a reversible selective inhibitor of viral protease and a potential blocker of viral replication, is indicated for the treatment of hepatitis C virus genotype 1 infection. In this study, the pharmacokinetic profile, safety, and tolerability of telaprevir and the effect of food on telaprevir exposure were evaluated in healthy Korean subjects, and compared with data from a previous study in Japanese male subjects.

Methods

The single ascending dose study was conducted in 3 dose-based groups (500, 750, and 1,250 mg, six subjects each) in a fasted state. In the multiple dose study, eight subjects in the fed state received 750 mg of telaprevir once on Day 1 and every 8 hours from Day 2 until the morning of Day 6. Serial blood samples for pharmacokinetic analysis were collected for up to 24 hours in the single ascending dose study and for 6 days in the multiple dose study. Individual pharmacokinetic parameters were calculated using a non-compartmental analysis method. Safety and tolerability profiles were evaluated throughout the study.

Results

Following multiple administrations of telaprevir, maximum plasma concentrations (C _max), area under the concentration–time curve (AUC _0–8), and C _trough (concentration at 8 h after drug administration) increased by ~2.41-fold. Compared to fasted state values, mean C _max and AUC _0–24 increased by 4.92- and 4.81-fold, respectively, after food intake. The C _max and AUC _inf of Korean subjects were 26%–34% higher than those of Japanese subjects; however, these differences were not clinically significant. All observed adverse events were mild and there was no discontinuation due to AEs.

Conclusion

In conclusion, the telaprevir’s pharmacokinetic characteristics were similar in Korean and Japanese subjects. Telaprevir was well tolerated in a single dose of up to 1,250 mg and in multiple doses of 750 mg.