title: Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men.
abstract: OBJECTIVE
  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.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Qin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016642:Bupropion / Q000493:pharmacokinetics*; D065702:Cytochrome P-450 CYP2B6; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D004177:Dipyrone; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating