Drug Design, Development and Therapy (Apr 2018)
Pharmacokinetic characteristics of telaprevir in healthy Korean male subjects and comparisons with Japanese
Abstract
Yewon Choi,1 Seonghae Yoon,1 Kyoko Matsumoto,2 Yoshiyasu Ohta,3 SeungHwan Lee,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Ikuyaku Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan; 3Sohyaku Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan 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 (Cmax), area under the concentration–time curve (AUC0–8), and Ctrough (concentration at 8 h after drug administration) increased by ~2.41-fold. Compared to fasted state values, mean Cmax and AUC0–24 increased by 4.92- and 4.81-fold, respectively, after food intake. The Cmax and AUCinf 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. Keywords: antiviral agents, hepatitis C virus, NS3/4A protease, ethnicity, pharmacokinetic profile
