Eichelbaum M, Reetz K P, Schmidt E K, Zekorn C
Xenobiotica. 1986 May;16(5):465-81. doi: 10.3109/00498258609050252.
The formation of the two major metabolites of the antiarrhythmic and oxytocic drug sparteine (2- and 5-dehydrosparteine) exhibits a genetic polymorphism. Two phenotypes, extensive (EM) and poor metabolizers (PM) are observed in the population. The frequency of the PM phenotype in various populations (Caucasian and Japanese) ranges from 2.3 to 9%. The metabolism of sparteine is determined by two allelic genes at a single gene locus. PM subjects are homozygous for an autosomal recessive gene. The metabolism of sparteine is predominantly under genetic control as treatment with drugs such as antipyrine and rifampicin known to induce oxidative drug metabolism elicited only marginal changes in sparteine metabolism. The formation of 2-dehydrosparteine in human liver microsomes from EM and PM subjects showed a more than 40-fold difference in Km between EM and PM subjects. However, Vmax-values were almost identical in both groups. These data indicate that the basis of the differences in oxidative capacity between EM and PM subjects is more likely to be due to a variant isozyme with defective catalytic properties than to a decreased amount of the isozyme.
抗心律失常及催产药物金雀花碱的两种主要代谢产物（2-脱氢金雀花碱和5-脱氢金雀花碱）的形成呈现出遗传多态性。在人群中观察到两种表型，即快代谢型（EM）和慢代谢型（PM）。不同人群（白种人和日本人）中PM表型的频率在2.3%至9%之间。金雀花碱的代谢由位于单个基因位点的两个等位基因决定。PM个体为常染色体隐性基因的纯合子。金雀花碱的代谢主要受遗传控制，因为已知诱导氧化药物代谢的药物如安替比林和利福平治疗仅引起金雀花碱代谢的微小变化。来自EM和PM个体的人肝微粒体中2-脱氢金雀花碱的形成显示，EM和PM个体之间的米氏常数（Km）相差40多倍。然而，两组的最大反应速度（Vmax）值几乎相同。这些数据表明，EM和PM个体之间氧化能力差异的基础更可能是由于具有催化特性缺陷的变异同工酶，而不是同工酶数量的减少。
