Hirai S, Hussain A, Haddadin M, Smith R B
J Pharm Sci. 1981 Apr;70(4):403-6. doi: 10.1002/jps.2600700416.
The contraceptive steroid ethinyl estradiol was extensively metabolized when given orally in solution to dogs. It was thought at first that metabolism occurred exclusively in the liver. However, use of standard equations to predict the oral bioavailability of drugs known to be metabolized by hepatic first pass resulted in significantly higher values than those obtained experimentally. To rationalize the data and to determine whether ethinyl estradiol also is metabolized in the gut wall during absorption, metabolism in rats was studied. The drug was administered in solution intraduodenally, intraportally, and intravenously as a bolus by first-order infusion. The results indicate that, in rats, 40% of the drug is metabolized by the gut wall and 79% of the drug in the portal blood is metabolized by the liver intraduodenal administration.
当以溶液形式口服给予犬类时，避孕甾体炔雌醇会被广泛代谢。起初人们认为代谢仅发生在肝脏。然而，使用标准方程来预测已知经肝脏首过代谢的药物的口服生物利用度，得出的值显著高于实验获得的值。为了使数据合理化并确定炔雌醇在吸收过程中是否也在肠壁中代谢，对大鼠的代谢情况进行了研究。通过一级输注以推注方式将该药物经十二指肠内、门静脉内和静脉内给予大鼠。结果表明，在大鼠中，40%的药物被肠壁代谢，经十二指肠给药时，门静脉血中79%的药物被肝脏代谢。
