{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:39:54Z","timestamp":1769222394372,"version":"3.49.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324,ss<\/jats:sub>\n            ), the steady-state maximum concentration of the drug in plasma (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max,ss<\/jats:sub>\n            ), and the steady-state concentration of the drug in plasma at 24 h (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>24,ss<\/jats:sub>\n            ) of 0.92 to 1.18 for (\n            <jats:italic>R<\/jats:italic>\n            )-methadone, (\n            <jats:italic>S<\/jats:italic>\n            )-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n            under registration no. NCT01637922.)\n          <\/jats:p>","DOI":"10.1128\/aac.04046-14","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T05:42:42Z","timestamp":1415684562000},"page":"498-504","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy"],"prefix":"10.1128","volume":"59","author":[{"given":"David","family":"Joseph","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Schobelock","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert R.","family":"Riesenberg","sequence":"additional","affiliation":[{"name":"Atlanta Center for Medical Research, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley D.","family":"Vince","sequence":"additional","affiliation":[{"name":"Vince &amp; Associates Clinical Research, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn R.","family":"Webster","sequence":"additional","affiliation":[{"name":"CRI Lifetree, Salt Lake City, Utah, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abidemi","family":"Adeniji","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabrouk","family":"Elgadi","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim (Canada) Ltd.\/Lt\u00e9e, Burlington, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglei","family":"Huang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22759"},{"key":"e_1_3_2_3_2","volume-title":"Hepatitis C fact sheet 164","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. Hepatitis C fact sheet 164. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/mediacentre\/factsheets\/fs164\/en\/index.html. Accessed 3 April 2014."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2008.02188.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(13)61415-4"},{"key":"e_1_3_2_6_2","unstructured":"Sabo JP Kashuba AD Ballow CH Haschke M Yong C MacGregor TR Li Y Kort J. 2012. Cytochrome P450 (CYP) interactions with the HCV protease inhibitor BI 201335 in healthy volunteers. Abstr 52nd Intersci Conf Antimicrob Agents Chemother abstr A-1248."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26858"},{"key":"e_1_3_2_8_2","volume-title":"Methadone (methadone HCl 10 mg\/mL) liquid prescribing information","author":"Roxane Laboratories, Inc","year":"2009","unstructured":"Roxane Laboratories, Inc. 2009. Methadone (methadone HCl 10 mg\/mL) liquid prescribing information. 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