title: Subacute imipramine: changes in single dose pharmacokinetics in rats.
abstract: 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.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D007099:Imipramine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007408:Intestinal Absorption; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D013997:Time Factors
chemical_list: D007099:Imipramine