Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men
Version of Record online: 13 NOV 2012
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 74, Issue 6, pages 999–1004, December 2012
How to Cite
Qin, W.-J., Zhang, W., Liu, Z.-Q., Chen, X.-P., Tan, Z.-R., Hu, D.-L., Wang, D., Fan, L. and Zhou, H.-H. (2012), Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men. British Journal of Clinical Pharmacology, 74: 999–1004. doi: 10.1111/j.1365-2125.2012.04304.x
- Issue online: 13 NOV 2012
- Version of Record online: 13 NOV 2012
- Accepted manuscript online: 23 APR 2012 02:30AM EST
- Received; 11 January 2012; Accepted; 12 April 2012; Accepted Article Published Online; 23 April 2012
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 Cmax, respectively. The corresponding values for 4-hydroxybupropion were 1.43 (1.28, 1.53) and 2.63 (2.07, 2.92). The t1/2 value was significantly increased for bupropion and decreased for 4-hydroxybupropion. The tmax 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.