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  • Title: The effect of estradiol-17 beta treatment on the metabolism and biliary excretion of phenytoin in the isolated perfused rat liver and in vivo.
    Author: Vore M, Montgomery C.
    Journal: J Pharmacol Exp Ther; 1980 Oct; 215(1):71-6. PubMed ID: 7452491.
    Abstract:
    The metabolism and biliary excretion of [14C]phenytoin (DPH) was examined in female control rats and in rats pretreated with estradiol-17 beta (E2) (1 mg/day s.c.) for 7 days. In the isolated perfused liver, the half-time of [14C]DPH in the perfusate was not altered by E2 treatment, nor was the rate of appearance and disappearance of 5-[14C]phenyl-5-para-hydroxyphenylhydantoin (HPPH), the major metabolite of DPH. Cumulative secretion of the glucuronide 4- and 6-fold, respectively, in E2-treated rats. Following administration of [14C]DPH (1 mg/kg i.v.) in vivo, the concentration of [14C]HPPH-glucuronide was significantly increased in the blood in E2-treated rats, although there was no significant decrease in the bile concentration or excretion rate of this metabolite. Bile flow averaged 50 and 35 microliters/min/kg in control and E2-treated rats, respectively. Following administration of [14C]HPPH (60 mg/kg i.v.) in vivo, the rate of disappearance of [14C]HPPH from the blood was increased in E2-treated rats. The concentration in bile (micromoles per milliliter) and biliary excretion rate (micromoles per minute per kilogram) of [14C]HPPH-glucuronide were significantly increased in E2-treated rats relative to controls. Maximal bile/blood concentration ratios of [14C]HPPH-glucuronide were 725 and 200 in control and E2-treated rats, respectively, indicating a decreased ability of the liver to concentrate the glucuronide conjugate in the bile following estrogen treatment.
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