Effects Of Metamizole On CYP2B6 Enzyme Activity And Its Relationship With CYP2B6 Genotype

Objective:Our objective was to study the effect of metamizole on bupropion(INN,amfebutamone) hydroxylation,a probe reaction for cytochrome P450(CYP) 2B6 activity related to different CYP2B6 haplotype groups.Methods:Sixteen unrelated healthy male volunteers with different CYP2B6 haplotypes(six CYP2B6^*1/^*1,six CYP2B6^*1/^*6,and four CYP2B6^*6/^*6) were selected to participate in this study. bupropion(150mg orally) and hydroxybupropion pharmacokinetics after coadministration of placebo and 0.5g metamizole tablets(three times daily orally for 4 days) were measured for up to 48h by liquid chromatography-mass spectrometry in a two-phase randomized crossover study.Results:The area under the plasma concentration-time curve ratio of hydroxybupropion:bupropion increasd 1.7-fold after metamizole administration(P=0.0001),and notably decreased the area under the curve AUC_0-∞(1075.1±181.2ng.h/ml VS 673.5±125.1 ng.h/ml,P=0.001) and Cmax(116.2±14.2 ng/ml VS 66.1±7.2 ng/ml,P=0.001) of Bupropion respectively;and significantly increased Cmax(436.7±52.8 ng/ml VS 656.5±72.9 ng/ml,P=0.007) of Hydroxybupropion,but not effect its AUC_0-∞.Conclusions:Metamizole significantly increased the CYP2B6-catalyzed bupropion hydroxylation,but not in an CYP2B6 haplotype-dependent manner.