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• W1652695956 abstract "WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite, 4‐hydroxybupropion, almost exclusively by CYP2B6. • Metamizole, a pyrazolone derivative with analgesic properties, was shown in an in vitro study to increase significantly the expression of CYP2B6 and bupropion hydroxylase activity. • The effect of metamizole on bupropion hydroxylation has not been investigated and drug interactions may occur between metamizole and bupropion. WHAT THIS PAPER ADDS • Oral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4‐hydroxybupropion, and significantly increased the CYP2B6‐catalyzed bupropion hydroxylation in all of the subjects. • Dosage adjustment of bupropion may be needed in patients when metamizole is concomitantly administered. AIMS This study aimed to investigate the effect of metamizole on bupropion hydroxylation related to different CYP2B6 genotype groups in healthy volunteers. METHODS Sixteen healthy male volunteers (6 CYP2B6 * 1/ * 1 , 6 CYP2B6 * 1/ * 6 and 4 CYP2B6 * 6/ * 6 ) received orally administered bupropion alone and during daily treatment with metamizole 1500 mg day –1 (500 mg tablet taken three times daily) for 4 days. Serial blood samples were obtained up to 48 h after each bupropion dose. RESULTS After metamizole treatment relative to bupropion alone, the geometric mean ratios (GMRs) and 90% confidence interval (CI) of the AUC(0,∞) ratio of 4‐hydroxybupropion over bupropion were 1.99 (1.57, 2.55) for the CYP2B6 * 1/ * 1 group, 2.15 (1.53, 3.05) for the CYP2B6 * 1/ * 6 group and 1.86 (1.36, 2.57) for the CYP2B6 * 6/ * 6 group. The GMRs and 90% CI of bupropion were 0.695 (0.622, 0.774) for AUC(0,∞) and 0.400 (0.353, 0.449) for C max , respectively. The corresponding values for 4‐hydroxybupropion were 1.43 (1.28, 1.53) and 2.63 (2.07, 2.92). The t 1/2 value was significantly increased for bupropion and decreased for 4‐hydroxybupropion. The t max values of bupropion and 4‐hydroxybupropion were both significantly decreased. The mean percentage changes in pharmacokinetic parameters among the CYP2B6 genotype groups were not significantly different. CONCLUSIONS Oral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4‐hydroxybupropion, and significantly increased the CYP2B6‐catalyzed bupropion hydroxylation in all of the subjects. Cautions should be taken when metamizole is co‐administered with CYP2B6 substrate drugs." @default.
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• W1652695956 date "2012-11-13" @default.
• W1652695956 modified "2023-10-18" @default.
• W1652695956 title "Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men" @default.
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• W1652695956 doi "https://doi.org/10.1111/j.1365-2125.2012.04304.x" @default.
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