The effect of estradiol-17 beta treatment on the metabolism and biliary excretion of phenytoin in the isolated perfused rat liver and in vivo.

TitleThe effect of estradiol-17 beta treatment on the metabolism and biliary excretion of phenytoin in the isolated perfused rat liver and in vivo.
Publication TypeJournal Article
Year of Publication1980
JournalThe Journal of pharmacology and experimental therapeutics
Volume215
Issue1
Pagination71-6
Date Published1980 Oct
ISSN0022-3565
AbstractThe 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.
URLhttp://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7452491
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/7452491?dopt=Abstract
Short TitleJ Pharmacol Exp Ther