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  • Title: Biotransformation and biliary excretion of imipramine in rats under various experimental conditions.
    Author: Gigon PL.
    Journal: Arch Int Pharmacodyn Ther; 1975 Aug; 216(2):315-27. PubMed ID: 1180619.
    Abstract:
    150 Minutes after intraperitoneal administration of 80 mg 14C-imipramine/kg to male rats, the percentage of the dose found in liver and determined as imipramine plus metabolites is 13-15% independently whether a bile fistula has been inserted or not. 1/4 of this percentage is located in the hepatic microsomal fraction. The simultaneous administration of pentobarbital and/or diphenylhydantoin does not alter these findings. The metabolite pattern, however, is shifted in favor of unmetabolized imipramine. In male rats without bile fistula, the enterohepatic circulation has no effect on the amount and the metabolite pattern of imipramine plus metabolites excreted into bile. In male rats with bile fistula, the biliary excretion of imipramine plus metabolites (87% as conjugated metabolites) over 8 h accounts for 26% of the dose (80 mg imipramine/kg) and follows first order kinetics. In female rats without bile fistula, the percentage of an identical imipramine dose found in liver after 150 min is only 7%. 1/7 of this percentage is located in the hepatic microsomal fraction. The percentage of unmetabolized imipramine in liver is double that found in male rats. Simultaneous administration of imipramine and pentobarbital at the same dosage as in male rats is lethal for female rats without bile fistula within 30 min.
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