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In Period 2 (Days 1\u201310), subjects received MMT<\/jats:styled-content> plus DNV<\/jats:styled-content>r 100\/100\u00a0mg twice\/day. Pharmacokinetic parameters for the total concentrations of (R<\/jats:styled-content>)\u2010 and (S<\/jats:styled-content>)\u2010methadone on Days \u22121 and 10 were determined using noncompartmental methods. Unbound (R<\/jats:styled-content>)\u2010 and (S<\/jats:styled-content>)\u2010methadone concentrations at 3\u00a0hours postdose were also assessed on Days \u22121 and 10. Geometric mean ratios (GMRs<\/jats:styled-content>) and 90% confidence intervals (CIs<\/jats:styled-content>) were used to compare steady\u2010state (R<\/jats:styled-content>)\u2010 and (S<\/jats:styled-content>)\u2010methadone pharmacokinetics when MMT<\/jats:styled-content> was administered with or without DNV<\/jats:styled-content>r. Methadone withdrawal was assessed using the S<\/jats:styled-content>ubjective O<\/jats:styled-content>piate W<\/jats:styled-content>ithdrawal Scale. Compared with MMT<\/jats:styled-content> alone, methadone AUC<\/jats:styled-content>tau<\/jats:sub> and C<\/jats:styled-content>max<\/jats:sub> GMR<\/jats:styled-content> (90% CI<\/jats:styled-content>) following coadministration with DNV<\/jats:styled-content>r were 1.02 (0.91\u20131.15) and 1.01 (0.90\u20131.13) for (R<\/jats:styled-content>)\u2010methadone, and 1.01 (0.90\u20131.13) and 0.99 (0.89\u20131.10) for (S<\/jats:styled-content>)\u2010methadone, respectively. Unbound (R<\/jats:styled-content>\u2010 and (S<\/jats:styled-content>)\u2010methadone concentrations were comparable with or without DNV<\/jats:styled-content>r. No instances of methadone withdrawal were reported. MMT in combination with DNV<\/jats:styled-content>r was well tolerated.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Coadministration of DNV<\/jats:styled-content>r with MMT<\/jats:styled-content> resulted in no significant pharmacokinetic interactions or signs of methadone withdrawal. No dosage adjustment is needed for MMT<\/jats:styled-content> when coadministered with DNV<\/jats:styled-content>r.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1341","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T19:38:37Z","timestamp":1376509117000},"page":"220-226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Ritonavir\u2010Boosted Danoprevir, a Potent Hepatitis C<\/scp> Virus Protease Inhibitor, on the Pharmacokinetics of Methadone in Healthy Subjects Undergoing Methadone Maintenance Therapy"],"prefix":"10.1002","volume":"34","author":[{"given":"Sebastian A.","family":"Moreira","sequence":"first","affiliation":[{"name":"Hoffmann\u2010La Roche Inc. Nutley New Jersey United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter N.","family":"Morcos","sequence":"additional","affiliation":[{"name":"Hoffmann\u2010La Roche Inc. 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