{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T16:32:59Z","timestamp":1757608379805,"version":"3.44.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Faldaprevir (FDV) is a novel NS3\/NS4A inhibitor used in the treatment of hepatitis C infection in an interferon-free regimen. This study evaluated the safety, tolerability, and pharmacokinetics of FDV following a single dose in healthy male subjects and assessed the effect of food on FDV bioavailability. In the placebo-controlled, randomized, single-blind, single-increasing-dose part of the study (Part 1), 64 healthy male subjects were randomized to receive FDV in PEG\/TRIS\/meglumine solution at one of eight dose levels (4\u20131,200\u00a0mg, n = 6 per dose group) or placebo (n = 2 per dose group). In Part 2, the effect of food on the relative bioavailability (rBA) of 480\u00a0mg FDV in solution was evaluated in an open-label, crossover comparison, with and without a high-fat breakfast, in an additional 10 subjects (8 FDV and 2 placebo). Following single doses of 4\u20131,200\u00a0mg FDV, geometric mean (gMean) C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0-inf<\/jats:sub> were 3.57\u201316500\u00a0ng\/mL and 254\u2013402000\u00a0h*ng\/mL, respectively, displaying more than dose-proportional increases in exposure. FDV was slowly absorbed, with gMean t<jats:sub>1\/2<\/jats:sub> and median t<jats:sub>max<\/jats:sub> of 15.5\u201339.2\u00a0h and 4.0\u201314.0\u00a0h, respectively; both were dose dependent. The urinary excretion of FDV was less than 0.1% of the dose. A high-fat breakfast increased systemic exposure to FDV in solution by 14%. FDV was generally well tolerated; subjects who experienced adverse events (AEs) recovered without sequelae, and no serious AEs were reported. Indirect (unconjugated) bilirubin of &amp;gt;3.0\u00a0mg\/dL was observed in two subjects at 480\u00a0mg and five subjects at 1,200\u00a0mg. In conclusion, at single doses of 4\u20131,200\u00a0mg in healthy male subjects, FDV showed dose-dependent pharmacokinetics and was generally considered safe and well tolerated. Food had no clinically relevant effect on the rBA of FDV.<\/jats:p>","DOI":"10.3389\/fphar.2025.1622249","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:14:26Z","timestamp":1756872866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, tolerability, and pharmacokinetics of faldaprevir after single increasing doses in healthy subjects"],"prefix":"10.3389","volume":"16","author":[{"given":"Chan-Loi","family":"Yong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Sennewald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Nehmiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"Quinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-349-10705-6_16","article-title":"Design of first-administration studies in healthy man","volume-title":"Early phase drug evaluation in man","author":"Broom","year":"1990"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1128\/aac.02156-13","article-title":"Mass balance and metabolite profiling of steady-state faldaprevir, a hepatitis C virus NS3\/4 protease inhibitor, in healthy male subjects","volume":"58","author":"Chen","year":"2014","journal-title":"Antimicrob. 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