Subacute imipramine: changes in single dose pharmacokinetics in rats. 1977

A R Beaubien, and L F Mathieu, and J A Huddleston, and H F James

Imipramine (10 mg/kg, p.o.) administered to male Wistar rats (133-178 g) twice daily for 3 weeks more than halved the control rate of body weight gain. A bile fistula was inserted after this period and 14C-imipramine (10 mg/kg, p.o.) was administered 14-18 hr after the final scheduled dose. Biliary excretion of radioactivity during the subsequent 50 min was decreased to 16% of control. Higher levels of gastrointestinal radioactivity (mainly in the stomach lumen) indicated a slower imipramine absorption rate in the subacute group. Liver metabolite ratios revealed that the treatment group had decreased rates of 2-hydroxylation and 10-hydroxylation, but not demethylation, of imipramine. After incubation of the 25-50 min bile sample with glusulase, bile-to-liver ratios of metabolites indicated a lower entry rate of imipramine, desmethylimipramine and 2-hydroxydesmethylimipramine, but not of 2-hydroxyimipramine or 10-hydroxyimipramine, into bile of the subacute imipramine group.

UI MeSH Term Description Entries
D007099 Imipramine The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. Imidobenzyle,Imizin,4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)-3-(10,11-dihydro-5H-dibenzo(b,f)azepin-5-yl)-N,N-dimethyl-1-propanamine (1:2),Imipramine Hydrochloride,Imipramine Monohydrochloride,Imipramine Pamoate,Janimine,Melipramine,Norchlorimipramine,Pryleugan,Tofranil
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007700 Kinetics The rate dynamics in chemical or physical systems.
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
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
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
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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