Biomaterial Database

The effect of pregnancy on the biliary excretion of [14C]phenytoin in the rat. 1979

M Vore, and E Soliven, and M Blunden

The biliary excretion of [14C]phenytoin (DPH) was examined in pregnant and nonpregnant female control rats. After administration of [14C]DPH (1 mg/kg i.v.), the bile concentration (nanomoles per milliliter) and biliary excretion (nanomoles per minute per kilogram) of the glucuronide conjugate of the major primary metabolite of DPH, 5-phenyl-5-p-hydroxyphenyl[4-14C] hydantoin ([14C)]HPPH), was significantly decreased at 15 and 30 min in pregnant rats relative to controls. Bile flow averaged 50 and 70 microliter/min/kg in control and pregnant rats, respectively. The concentration in blood of [14C]HPPH-glucuronide was increased 2 to 6-fold in pregnant rats relative to controls. After administration of [14C]HPPH (10 mg/kg i.v.), the disappearance of [14C]HPPH from the blood, biliary excretion and bile concentration of [14C]HPPH-glucuronide were very similar in control and pregnant rats. The blood concentration of [14C]HPPH-glucuronide was elevated 2 to 6-fold in pregnant rats and the half-life was increased from 43 min in controls to 70 min in pregnant rats. Maximal bile/blood concentration ratios of [14C]HPPH-glucuronide were 630 and 300 in control and pregnant rats, respectively, indicating a decreased ability of the liver to concentrate the glucuronide in the bile in pregnancy.

UI	MeSH Term	Description	Entries
D010672	Phenytoin	An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.	Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011270	Pregnancy, Animal	The process of bearing developing young (EMBRYOS or FETUSES) in utero in non-human mammals, beginning from FERTILIZATION to BIRTH.	Animal Pregnancies,Animal Pregnancy,Pregnancies, Animal
D005260	Female		Females
D005965	Glucuronates	Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.	Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006900	Hydroxylation	Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)	Hydroxylations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001646	Bile	An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.	Biliary Sludge,Sludge, Biliary
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus