{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T14:23:56Z","timestamp":1769351036448,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Faldaprevir (FDV) is an investigational NS3\/NS4A protease inhibitor for chronic hepatitis C. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of FDV after multiple rising doses in healthy male volunteers and subjects with Gilbert syndrome (GS). In this randomized, double\u2010blind, placebo\u2010controlled study, healthy males received once\u2010daily oral FDV (20, 48, 120\u00a0mg [\n                    <jats:italic>n<\/jats:italic>\n                    = 6 per group], 240\u00a0mg [\n                    <jats:italic>n<\/jats:italic>\n                    = 5]), or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    = 7). A single dose was given on Day 1, followed by a 72\u2010h washout and 21 days of dosing from day 4. Separately, 9 GS subjects received open\u2010label FDV 240\u00a0mg daily for 28 days. PK was assessed after the first and last doses; safety was evaluated throughout. FDV showed greater than dose\u2010proportional increases in exposure (gMean\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max,ss<\/jats:sub>\n                    : 99\u20135360\u00a0ng\/mL; AUC\n                    <jats:italic>\n                      <jats:sub>\u03c4<\/jats:sub>\n                    <\/jats:italic>\n                    <jats:sub>,ss<\/jats:sub>\n                    : 1740\u201350,100 h\u00b7ng\/mL) and time\u2010dependent PK with a linearity index &gt;1. Mean\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    was 20\u201330 h; steady state was reached in 6\u20137 days with an accumulation ratio of 2.8\u20133.1. FDV exposure in GS subjects was similar but slightly lower. Total bilirubin increased dose\u2010dependently, with higher indirect bilirubin in GS subjects. FDV exhibited non\u2010linear, time\u2010dependent PK and was generally well tolerated up to 240\u00a0mg\/day in subjects with or without GS.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1601","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T18:39:28Z","timestamp":1755887968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Pharmacodynamics of Faldaprevir Following Multiple Oral Rising Doses in Healthy Volunteers and Subjects with Gilbert's Syndrome"],"prefix":"10.1002","volume":"15","author":[{"given":"Mabrouk","family":"Elgadi","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan\u2010Loi","family":"Yong","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wruck","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis L","family":"Cooper","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital Research Institute  Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie","family":"Quinson","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglei","family":"Huang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00787-10"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02156-13"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.418"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.931"},{"issue":"5","key":"e_1_2_8_6_1","first-page":"189","article-title":"Effect of itraconazole on the pharmacokinetics of faldaprevir in healthy subjects","volume":"76","author":"Huang F","year":"2021","journal-title":"Die Pharm"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.024"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04383-14"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12693"},{"key":"e_1_2_8_10_1","unstructured":"NCT02593162.Trek therapeutics: a study of faldaprevir ribavirin and TD\u20106450 in participants with genotype 4 hepatitis C virus infection. 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