Pharmacokinetic characteristics of telaprevir in healthy Korean male subjects and comparisons with Japanese
Received 2 August 2017
Accepted for publication 6 November 2017
Published 30 April 2018 Volume 2018:12 Pages 1045—1051
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Anastasios Lymperopoulos
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
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