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  • Title: First-pass metabolism of ethinyl estradiol in dogs and rats.
    Author: Hirai S, Hussain A, Haddadin M, Smith RB.
    Journal: J Pharm Sci; 1981 Apr; 70(4):403-6. PubMed ID: 7229953.
    Abstract:
    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.
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