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- Title
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.
- Authors
Zhao, Xia; Wang, Zining; Wang, Yukun; Zhang, Hong; Blode, Hartmut; Yoshikawa, Kenichi; Becker, Corina; Unger, Sigrun; Frey, Reiner; Cui, Yimin
- Abstract
<bold>Background and Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ASIANS; COMPARATIVE studies; HETEROCYCLIC compounds; RESEARCH methodology; MEDICAL cooperation; RESEARCH; SMOKING; EVALUATION research; RANDOMIZED controlled trials; HUMAN research subjects; BLIND experiment
- Publication
Clinical Pharmacokinetics, 2016, Vol 55, Issue 5, p615
- ISSN
0312-5963
- Publication type
journal article
- DOI
10.1007/s40262-015-0337-4