Biomaterial Database

Effect of isoniazid on the metabolism of 14C-diphenylhydantoin in rats. 1978

H S Buttar, and L T Wong, and J H Moffatt

The effect of isoniazid (INH, 0,5, 10 or 20 mg/kg; p.o.) on the metabolic disposition of 14C-diphenylhydantoin (DPH, 50 mg/kg; i.v.) was studied in rats for 5 hours. The disappearance rate of 14C from the blood was similar up to 2 hr, whereas at 3 hr the levels of 14C were significantly higher in 10 and 20 mg/kg INH-treated rats than the controls. While the urinary excretion remained virtually unaltered, the fecal excretion of 14C was significantly reduced in the presence of INH. Increasing doses of INH caused a corresponding increase in the concentration of 14C in the blood, plasma, liver, kidney, lung, brain, skeletal muscle, fat, heart, tests and spleen. At the end of 5 hr, about 74% of the radioactivity was present as unmetabolized DPH in the plasma of control animals; this was increased significantly in a dose-related manner by INH, reaching a concentration of 93% at the highest doses of INH administered. The results suggest that the INH-induced elevation of DPH-derived 14C in plasma and its marked accumulation in other tissues is due to inhibition of both the p-hydroxylation of DPH and the glucuronidation of its metabolites.

UI	MeSH Term	Description	Entries
D007538	Isoniazid	Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.	Isonicotinic Acid Hydrazide,Ftivazide,Isonex,Isonicotinic Acid Vanillylidenehydrazide,Phthivazid,Phthivazide,Tubazide,Acid Vanillylidenehydrazide, Isonicotinic,Hydrazide, Isonicotinic Acid,Vanillylidenehydrazide, Isonicotinic Acid
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
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
D001826	Body Fluids	Liquid components of living organisms.	Body Fluid,Fluid, Body,Fluids, Body
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D005243	Feces	Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
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
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
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