{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T02:28:47Z","timestamp":1700447327529},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T00:00:00Z","timestamp":1532390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>We conducted two phase I trials to evaluate the pharmacokinetic interactions between elbasvir (EBR), grazoprevir (GZR), and methadone (MK\u20108742\u2010P010 and MK\u20105172\u2010P030) in non\u2010hepatitis C virus (HCV)\u2010infected participants on methadone maintenance therapy. Coadministration of EBR or GZR with methadone had no clinically meaningful effect on EBR, GZR, or methadone pharmacokinetics. The geometric mean ratios (GMRs) for R\u2010 and S\u2010methadone AUC<jats:sub>0\u201024<\/jats:sub> were 1.03 (90% confidence interval (CI), 0.92<\/jats:bold>\u2013<jats:bold>1.15) and 1.09 (90% CI, 0.94<\/jats:bold>\u2013<jats:bold>1.26) in the presence\/absence of EBR; and 1.09 (90% CI, 1.02<\/jats:bold>\u2013<jats:bold>1.17) and 1.23 (90% CI, 1.12<\/jats:bold>\u2013<jats:bold>1.35) in the presence\/absence of GZR. The GMRs for EBR and GZR AUC<jats:sub>0\u201024<\/jats:sub> in participants receiving methadone relative to a healthy historical cohort not receiving methadone were 1.20 (90% CI, 0.94<\/jats:bold>\u2013<jats:bold>1.53) and 1.03 (90% CI, 0.76<\/jats:bold>\u2013<jats:bold>1.41), respectively. These results indicate that no dose adjustment is required for individuals with HCV infection receiving stable methadone therapy and the EBR\/GZR fixed\u2010dose regimen<\/jats:bold>.<\/jats:p>","DOI":"10.1111\/cts.12564","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T02:24:00Z","timestamp":1532485440000},"page":"553-561","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy"],"prefix":"10.1111","volume":"11","author":[{"given":"Hwa\u2010Ping","family":"Feng","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zifang","family":"Guo","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luzelena","family":"Caro","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William L.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"},{"name":"Alexion Pharmaceuticals, Inc.  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Panebianco","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavan","family":"Vaddady","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Reitmann","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Jumes","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Wolford","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain","family":"Fraser","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"},{"name":"Abide Therapeutics, Inc.  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Valesky","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Martinho","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan R.","family":"Butterton","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Webster","sequence":"additional","affiliation":[{"name":"CRI Lifetree Clinical Research  Salt Lake City Utah USA"},{"name":"PRA Health Sciences  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy W.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,24]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/155.7.645"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61097-0"},{"key":"e_1_2_9_4_1","volume-title":"US package insert","author":"ZEPATIER","year":"2017"},{"key":"e_1_2_9_5_1","volume-title":"EU summary of product characteristics","author":"ZEPATIER","year":"2016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00324-12"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201300343"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml300017p"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0785"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.04.009"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ722"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00114-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00349-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1975.tb09391.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.05.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00921.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211797440203"},{"key":"e_1_2_9_18_1","volume-title":"US package insert","author":"Dolophine hydrochloride CII (methadone hydrochloride tablets, USP)","year":"2006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00272.x"},{"key":"e_1_2_9_20_1","unstructured":"United States Food and Drug Administration.2016.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2016\/208261Orig1s000ClinPharmR.pdf. Accessed 31 Jan 2018."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-0816"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcts.12564","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T11:54:26Z","timestamp":1694865266000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,24]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/cts.12564"],"URL":"https:\/\/doi.org\/10.1111\/cts.12564","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,24]]},"assertion":[{"value":"2017-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}