Biomaterial Database

Distribution of phenobarbital and phenytoin in pregnant rats and their fetuses. 1991

C L DeVane, and J W Simpkins, and S A Stout

Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville 32610.

Studies were conducted to determine the extent of fetal exposure to phenobarbital (PB) and phenytoin (PHT) in pregnant rats. Two groups of rats determined to be in the third week of pregnancy received 30 mg/kg as a single intraperitoneal (i.p.) dose of either PB or PHT. At various times (from 15 min to 48 h for PB and from 20 min to 16 h for PHT), the rats were killed and whole blood, plasma, maternal brain, fetal brain and liver, whole fetuses, and placentas were rapidly collected. Concentrations of PB, PHT, and its major metabolite, p-hydroxyphenytoin (HPPH), were measured by high-performance liquid chromatography (HPLC). PB and PHT appeared rapidly in plasma and all tissues; the maximum HPPH concentrations appeared much later. The highest PB concentrations were detected in plasma, followed by placenta, whole fetus, maternal brain, fetal liver, and fetal brain. In contrast, PHT concentrations were higher in fetal brain and liver than in whole fetuses. HPPH concentrations were much lower than PHT and were not detected in maternal brain. These results show that PB and PHT readily distribute to the rat fetus, that drug distribution within the fetus is regional, and that changes in maternal plasma concentrations of these antiepileptic drugs (AEDs) are accompanied by parallel changes in fetal tissue.

UI	MeSH Term	Description	Entries
D008431	Maternal-Fetal Exchange	Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission.	Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
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
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D005260	Female		Females
D005333	Fetus	The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.	Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
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
D014018	Tissue Distribution	Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.	Distribution, Tissue,Distributions, Tissue,Tissue Distributions