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Silibinin affects the pharmacokinetics of methadone in rats
Author(s) -
Pan PeiPei,
Wang Jun,
Luo Jun,
Wang ShuangHu,
Zhou YunFang,
Chen SaiZhen,
Du Zhou
Publication year - 2018
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2235
Subject(s) - silibinin , methadone , pharmacokinetics , pharmacology , chemistry , medicine , metabolite
The aim of the present study was to investigate the pharmacokinetic effect of silibinin on methadone in rats. Twenty‐four male Sprague–Dawley rats were randomly divided into 4 groups: control group, single dose of 100 mg/kg group, multiple doses of 100 mg/kg group, and multiple doses of 30 mg/kg group. A single dose of 6 mg/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‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), were determined by ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Compared with the control group (without silibinin), both 30 and 100 mg/kg silibinin significantly increased the C max of methadone, but only 100 mg/kg silibinin significantly increased the AUC (0‐t) of methadone and decreased its clearance. Pharmacokinetics parameters of EDDP were not altered by 30 mg/kg silibinin; its T max was decreased by 100 mg/kg silibinin and the C max was increased by single dose of 100 mg/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.