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  • Title: Effects of ethinyl estradiol on pharmacokinetics of meperidine and pentobarbital in the rat.
    Author: Knodell RG, Allen RC, Kyner WT.
    Journal: J Pharmacol Exp Ther; 1982 Apr; 221(1):1-6. PubMed ID: 7062276.
    Abstract:
    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.
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