Knodell R G, Allen R C, Kyner W T
J Pharmacol Exp Ther. 1982 Apr;221(1):1-6.
Effects of estrogen administration on in vivo hepatic microsomal drug metabolism have been frequently assessed, but there has been little study of the effects of estrogen treatment on in vivo drug pharmacokinetics. After administration of ethinyl estradiol (5 mg/kg daily for 5 days), meperidine and pentobarbital pharmacokinetics were determined both in vivo and in the isolated perfused rat liver. Estrogen pretreatment caused a 45% reduction in systemic meperidine clearance in vivo and perfusate disappearance of both meperidine and its major metabolite, normeperidine, was slower in isolated liver experiments from ethinyl estradiol-treated animals as compared with propylene glycol-treated controls. In contrast to meperidine, clearance of pentobarbital was not decreased by estrogen treatment. These studies demonstrate that estrogen treatment singularly can alter drug pharmacokinetics in the rat and raise the question as to whether clinically important alterations in drug pharmacokinetics occur in humans receiving estrogen therapy.
雌激素给药对体内肝微粒体药物代谢的影响已得到频繁评估，但雌激素治疗对体内药物药代动力学的影响却鲜有研究。给予乙炔雌二醇（每日5毫克/千克，持续5天）后，在体内和离体灌注大鼠肝脏中测定了哌替啶和戊巴比妥的药代动力学。雌激素预处理使体内哌替啶的全身清除率降低了45%，在离体肝脏实验中，与丙二醇处理的对照组相比，乙炔雌二醇处理的动物体内哌替啶及其主要代谢物去甲哌替啶的灌流液消失速度更慢。与哌替啶不同，雌激素治疗并未降低戊巴比妥的清除率。这些研究表明，雌激素治疗单独即可改变大鼠体内的药物药代动力学，并引发了一个问题，即接受雌激素治疗的人类是否会发生具有临床重要性的药物药代动力学改变。
