{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:07:35Z","timestamp":1760044055967,"version":"3.41.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg;<jats:italic>n<\/jats:italic>= 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg;<jats:italic>n<\/jats:italic>= 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUC\u03c4) or maximum concentration in plasma (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (<jats:italic>R<\/jats:italic>- and<jats:italic>S<\/jats:italic>-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUC\u03c4 for<jats:italic>R<\/jats:italic>-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24),<jats:italic>S<\/jats:italic>-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUC\u03c4 was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments.<\/jats:p>","DOI":"10.1128\/aac.00478-15","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T02:44:58Z","timestamp":1435632298000},"page":"5503-5510","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Assessment of Drug-Drug Interactions between Daclatasvir and Methadone or Buprenorphine-Naloxone"],"prefix":"10.1128","volume":"59","author":[{"given":"T.","family":"Garimella","sequence":"first","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Wang","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.-L.","family":"Luo","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Wastall","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kandoussi","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"DeMicco","sequence":"additional","affiliation":[{"name":"Anaheim Clinical Trials, Anaheim, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. D.","family":"Bruce","sequence":"additional","affiliation":[{"name":"Cornell Scott-Hill Health Center and Yale University, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Hwang","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Bertz","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Bifano","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research &amp; Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306218"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.057"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61059-X"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402338"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61097-0"},{"key":"e_1_3_2_9_2","volume-title":"75th Annu Meet College Problems Drug Dependence","author":"Nyandindi C","year":"2013","unstructured":"Nyandindi C, Mbwambo J, McCurdy S, Lambdin B, Copenhaver M, Bruce R. 2013. Prevalence of HIV, hepatitis C and depression among people who inject drugs in the Kinondoni municipality in Dar Es Salaam, Tanzania, abstr 473\/poster 113. 75th Annu Meet College Problems Drug Dependence, San Diego, CA, 15 to 20 June 2013."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2009.10.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/med\/9780195399349.003.0046","volume-title":"Neurology of AIDS","author":"Bruce RD","year":"2011","unstructured":"Bruce RD. 2011. Medical interventions for addiction, p 581\u2013600. In Gendelman HE, Grant I, Everall IP, Fox HS, Gelband HA, Lipton SA, Swindells S (ed), Neurology of AIDS, 3rd ed. Oxford University Press, New York, NY.","edition":"3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.06.024"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0022-3565(25)03418-4","article-title":"Pharmacologic comparison of the optical isomers of methadon","volume":"93","author":"Scott CC","year":"1948","unstructured":"Scott CC, Robbins EB, Chen KK. 1948. Pharmacologic comparison of the optical isomers of methadon. J Pharmacol Exp Ther 93:282\u2013286.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0022-3565(25)28669-4","article-title":"Localization of d- and l-methadone after intraventricular injection into rat brains","volume":"175","author":"Ingoglia NA","year":"1970","unstructured":"Ingoglia NA, Dole VP. 1970. Localization of d- and l-methadone after intraventricular injection into rat brains. J Pharmacol Exp Ther 175:84\u201387.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.6.742"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/chir.10303"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.117580"},{"key":"e_1_3_2_18_2","first-page":"818","article-title":"Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4","volume":"26","author":"Kobayashi K","year":"1998","unstructured":"Kobayashi K, Yamamoto T, Chiba K, Tani M, Shimada N, Ishizaki T, Kuroiwa Y. 1998. Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4. Drug Metab Dispos 26:818\u2013821.","journal-title":"Drug Metab Dispos"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.003681"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.2174\/187231209788654117"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.029546"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08960"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(14)60113-6"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24609"},{"key":"e_1_3_2_25_2","volume-title":"8th Int Workshop Clin Pharmacol Hepatitis Ther, Cambridge, MA, 26 to 27 June 2013","author":"Bifano M","year":"2013","unstructured":"Bifano M, Sevinsky H, Stonier M, Jiang H, Bertz RJ. 2013. Daclatasvir, an HCV NS5A replication complex inhibitor, has minimal effect on pharmacokinetics of midazolam, a sensitive probe for cytochrome P450 3A4, abstr O_15. 8th Int Workshop Clin Pharmacol Hepatitis Ther, Cambridge, MA, 26 to 27 June 2013. (Presentation available at http:\/\/regist2.virology-education.com\/2013\/8hepcam\/docs\/21_Bertz.pdf.)"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2003.10400007"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3109\/00952998709001515"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000183628.20041.f2"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2012.05.028"},{"key":"e_1_3_2_30_2","first-page":"1","article-title":"Sample size determination for bioequivalence assessment by means of confidence intervals","volume":"29","author":"Diletti E","year":"1991","unstructured":"Diletti E, Hauschke D, Steinijans VW. 1991. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol 29:1\u20138.","journal-title":"Int J Clin Pharmacol Ther Toxicol"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2718"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-015-0279-5"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2674"},{"key":"e_1_3_2_34_2","unstructured":"Song I Jerva F Zong J Choukour M Wynne B Buchanan A Eley T Huang S Ross L. 2015. Evaluation of drug interactions between dolutegravir and daclatasvir in healthy subjects abstr 79. 16th Int Workshop Clin Pharmacol HIV and Hepatitis Ther Washington DC 26 to 28 May 2015."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.01.026"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.029"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0022-3565(25)24425-1","article-title":"Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling","volume":"272","author":"Ohtani M","year":"1995","unstructured":"Ohtani M, Kotaki H, Sawada Y, Iga T. 1995. Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther 272:505\u2013510.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0022-3565(24)36604-2","article-title":"Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine","volume":"281","author":"Ohtani M","year":"1997","unstructured":"Ohtani M, Kotaki H, Nishitateno K, Sawada Y, Iga T. 1997. Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine. J Pharmacol Exp Ther 281:428\u2013433.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0b013e31806c9202"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0022-3565(24)29586-0","article-title":"Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist","volume":"297","author":"Huang P","year":"2001","unstructured":"Huang P, Kehner GB, Cowan A, Liu-Chen LY. 2001. Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther 297:688\u2013695.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.08.002"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1521-0391.2013.12052.x"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00478-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00478-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T22:51:42Z","timestamp":1748472702000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00478-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":41,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1128\/AAC.00478-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.00478-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"2015-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}