1. Academic Validation
  2. Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study

Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study

  • Clin Pharmacokinet. 2016 May;55(5):615-24. doi: 10.1007/s40262-015-0337-4.
Xia Zhao 1 Zining Wang 2 Yukun Wang 3 Hong Zhang 3 Hartmut Blode 3 Kenichi Yoshikawa 4 Corina Becker 5 Sigrun Unger 6 Reiner Frey 5 Yimin Cui 2
Affiliations

Affiliations

  • 1 Peking University First Hospital, No. 6 Da Hong Luo Chang Street, Beijing, 100034, China. zxyjk@126.com.
  • 2 Peking University First Hospital, No. 6 Da Hong Luo Chang Street, Beijing, 100034, China.
  • 3 Clinical Pharmacology Asia, Bayer HealthCare Co. Ltd., Beijing, China.
  • 4 Clinical Pharmacology Asia, Bayer Yakuhin, Ltd., Osaka, Japan.
  • 5 Clinical Pharmacology, Bayer Pharma AG, Pharma Research Center, 42113, Wuppertal, Germany.
  • 6 Global Biostatistics, Bayer Pharma AG, Pharma Research Center, Wuppertal, Germany.
Abstract

Background and objectives: The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of riociguat after single and multiple oral doses of 1 or 2 mg three times daily (tid), and to determine the effect of smoking on riociguat pharmacokinetics in Chinese men.

Methods: In a randomized, double-blind, placebo-controlled, single-center study stratified for smokers and non-smokers, healthy Chinese men aged 18-45 years received two riociguat doses: Dose Step 1 (1 mg) then Dose Step 2 (2 mg) conducted after the safety and tolerability at Dose Step 1 was confirmed. For each step, 12 subjects received riociguat and six received placebo. A single dose was given on Day 1, followed by a 48-h pharmacokinetic profile. Multiple-dose treatment tid was then given for 6 days (Days 3-8), with a last single dose on Day 9, followed by a 72-h pharmacokinetic profile. Primary outcomes were pharmacokinetic parameters for riociguat after single and multiple dosing.

Results: Thirty-six subjects (18 smokers; 18 non-smokers) were randomized and provided valid pharmacokinetic data. Riociguat and its pharmacologically active metabolite M1 (BAY 60-4552) showed nearly dose-proportional pharmacokinetics. Accumulation was minimal in smokers and approximately two-fold in non-smokers. Exposure for riociguat was decreased by ≥60% in smokers. No serious or significant adverse events occurred during the study.

Conclusions: Riociguat pharmacokinetics showed dose proportionality in healthy Chinese men, as previously demonstrated in healthy white male individuals. Exposure to riociguat was substantially decreased in smokers compared with non-smokers. Riociguat was well tolerated in Chinese men.

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