Skett P, Paterson P
Biochem Pharmacol. 1985 Oct 1;34(19):3533-6. doi: 10.1016/0006-2952(85)90729-4.
This study investigates the sex-dependence of the effects of microsomal enzyme inducers (phenobarbitone, isosafrole and ethanol) on the hepatic phase I metabolism of lignocaine and imipramine. It is shown that all of the inducers exert sex-dependent effects on the enzymes activities known to be sex related in the rat, e.g. lignocaine N-deethylase activity is decreased by phenobarbitone pretreatment in the male but increased by the same treatment in the female. The inducers tend to decrease the sex differences seen in untreated animals. Ethanol may give this effect by its action of decreasing serum testosterone levels but the mechanism of action of the other compounds is uncertain. It is possible that the sex-dependent cytochrome P-450 species are selectively sensitive to the action of the compounds in terms of induction, repression or inhibition. It is clear, however, that the effects of the pretreatments are related to the sex differences in phase I metabolism in the rat.
本研究调查了微粒体酶诱导剂（苯巴比妥、异黄樟素和乙醇）对利多卡因和丙咪嗪肝脏I相代谢影响的性别依赖性。结果表明，所有诱导剂对大鼠体内已知与性别相关的酶活性均产生性别依赖性影响，例如，苯巴比妥预处理可降低雄性大鼠利多卡因N-脱乙基酶活性，但却能提高雌性大鼠的该酶活性。诱导剂往往会减少未处理动物中观察到的性别差异。乙醇可能通过降低血清睾酮水平发挥此作用，但其他化合物的作用机制尚不确定。就诱导、抑制或抑制而言，性别依赖性细胞色素P-450种类可能对这些化合物的作用具有选择性敏感性。然而，很明显，预处理的效果与大鼠I相代谢中的性别差异有关。
