{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T18:25:13Z","timestamp":1758479113283},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>Asunaprevir (BMS\u2010650032, ASV) is a potent, selective hepatitis C virus (HCV) NS3 protease inhibitor in clinical evaluation for chronic hepatitis C treatment. ASV pharmacokinetics were evaluated in four single\u2010 and multiple\u2010ascending\u2010dose studies in healthy subjects or subjects with HCV genotype 1 infection and in human mass balance and food\u2010effect studies. Median T<jats:sub>max<\/jats:sub> was 2\u20134\u2009hours. Although T<jats:sub>\u00bd<\/jats:sub> was 14\u201323\u2009hours, oral clearance was high (302\u2013668\u2009L\/h at doses \u2265100\u2009mg). Steady state was achieved by Day 7. The ASV dose\u2013exposure relationship was disproportionate at doses &lt;200\u2009mg but largely proportional for C<jats:sub>max<\/jats:sub> and AUC at clinically relevant doses of 200\u2013600\u2009mg (capsule). Following multiple doses, the accumulation index for AUC<jats:sub>[TAU]<\/jats:sub> and C<jats:sub>min<\/jats:sub> was lower at doses \u2265200\u2009mg, suggestive of possible auto\u2010induction. ASV exposure increased when administered as a solution (vs. suspension) or with a high\u2010fat meal; the effect was greater for C<jats:sub>max<\/jats:sub> than AUC, suggesting a saturable first\u2010pass process, the mechanism of which remains to be defined. The apparent complexities of ASV pharmacokinetics will be further explored; nevertheless, data from these studies and antiviral activity in phase 2a\/2b studies support further development. Clinical studies are ongoing with ASV in combination with other antivirals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.52","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T13:55:11Z","timestamp":1376661311000},"page":"316-327","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS\u2010650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C"],"prefix":"10.1002","volume":"2","author":[{"given":"Timothy","family":"Eley","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Hopewell NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"He","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Hopewell NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Pang","family":"Huang","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenying","family":"Li","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Pasquinelli","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Hopewell NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. David","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis M.","family":"Grasela","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Hopewell NJ USA"},{"name":"Bristol\u2010Myers Squibb, Research and Development Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Bertz","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb, Research and Development Hopewell NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2893.2003.00487.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02537.x"},{"key":"e_1_2_7_4_1","unstructured":"World Health Organization. Hepatitis C key facts. Available from (http:\/\/www.who.int\/mediacentre\/factsheets\/fs164\/en\/). Updated 2011. Accessed December 1 2011."},{"key":"e_1_2_7_5_1","unstructured":"World Health Organization. Global alert and response (GAR)\u2014hepatitis C. Available from (http:\/\/www.who.int\/csr\/disease\/hepatitis\/whocdscsrlyo2003\/en\/index4.html). Updated 2011. 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