{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:24:53Z","timestamp":1760487893962,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T00:00:00Z","timestamp":1503532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Enze Scientific Research Fund","award":["15EZC3"],"award-info":[{"award-number":["15EZC3"]}]},{"name":"Clinical Pharmacy Research of Zhejiang Province of Chinese Integrative Medicine","award":["2014LYK011"],"award-info":[{"award-number":["2014LYK011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>The aim of the present study was to investigate the pharmacokinetic effect of silibinin on methadone in rats. Twenty\u2010four male Sprague\u2013Dawley rats were randomly divided into 4 groups: control group, single dose of 100\u00a0mg\/kg group, multiple doses of 100\u00a0mg\/kg group, and multiple doses of 30\u00a0mg\/kg group. A single dose of 6\u00a0mg\/kg methadone was administrated to rats orally without or with silibinin. Plasma samples were collected via tail vein at different time points and concentrations of methadone and its metabolite, 2\u2010ethylidene\u20101,5\u2010dimethyl\u20103,3\u2010diphenylpyrrolidine (EDDP), were determined by ultra performance liquid chromatography\u2013tandem mass spectrometry (UPLC\u2013MS\/MS). Compared with the control group (without silibinin), both 30 and 100\u00a0mg\/kg silibinin significantly increased the C<jats:sub>max<\/jats:sub> of methadone, but only 100\u00a0mg\/kg silibinin significantly increased the AUC<jats:sub>(0\u2010t)<\/jats:sub> of methadone and decreased its clearance. Pharmacokinetics parameters of EDDP were not altered by 30\u00a0mg\/kg silibinin; its T<jats:sub>max<\/jats:sub> was decreased by 100\u00a0mg\/kg silibinin and the C<jats:sub>max<\/jats:sub> was increased by single dose of 100\u00a0mg\/kg silibinin. It is concluded that silibinin significantly altered the pharmacokinetics of methadone in rats by increasing the exposure of methadone. Further investigations in human should be conducted. Therapeutic drug monitoring of methadone in individuals undergoing methadone maintenance therapy is recommended when silibinin is concomitant.<\/jats:p>","DOI":"10.1002\/dta.2235","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T20:22:50Z","timestamp":1498162970000},"page":"557-561","source":"Crossref","is-referenced-by-count":7,"title":["Silibinin affects the pharmacokinetics of methadone in rats"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-4288","authenticated-orcid":false,"given":"Pei\u2010Pei","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pharmacy Taizhou Central Hospital  Taizhou Zhejiang PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital  Wenzhou Zhejiang 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