{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:01:12Z","timestamp":1772823672167,"version":"3.50.1"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"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":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of\n            <jats:italic>R-<\/jats:italic>\n            and\n            <jats:italic>S<\/jats:italic>\n            -methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound\n            <jats:italic>R<\/jats:italic>\n            -methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            ), the maximum plasma concentration (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) for\n            <jats:italic>R<\/jats:italic>\n            -methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ratio of\n            <jats:italic>S<\/jats:italic>\n            -methadone\/\n            <jats:italic>R<\/jats:italic>\n            -methadone was not altered. The median unbound percentage of\n            <jats:italic>R<\/jats:italic>\n            -methadone increased by 26% in the presence of telaprevir. The\n            <jats:italic>R<\/jats:italic>\n            -methadone median (absolute) unbound\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            values in the absence (10.63 ng\/ml) and presence (10.45 ng\/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total\n            <jats:italic>R<\/jats:italic>\n            -methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound\n            <jats:italic>R<\/jats:italic>\n            -methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.)\n          <\/jats:p>","DOI":"10.1128\/aac.02262-12","type":"journal-article","created":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T01:07:32Z","timestamp":1363050452000},"page":"2304-2309","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Pharmacokinetic Interaction between Telaprevir and Methadone"],"prefix":"10.1128","volume":"57","author":[{"given":"Rolf","family":"van Heeswijk","sequence":"first","affiliation":[{"name":"Janssen Infectious Diseases BVBA, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Verboven","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Vandevoorde","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Vinck","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Snoeys","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Griet","family":"Boogaerts","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"De Paepe","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodica","family":"Van Solingen-Ristea","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Titusville, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Witek","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Titusville, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun","family":"Garg","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2011.03765.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2008.02188.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012912"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014463"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013086"},{"key":"e_1_3_2_7_2","first-page":"159","article-title":"Methadone: pharmacokinetics and pharmacodynamics of an opiate","volume":"38","author":"Jage J","year":"1989","unstructured":"JageJ. 1989. 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