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Xenobiotica
the fate of foreign compounds in biological systems
Volume 5, 1975 - Issue 10
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Research Article

Effect of Diphenylhydantoin on the Biotransformation and Biliary Excretion of Impramine in Rats

Pages 585-594 | Received 20 Aug 1974, Accepted 30 Mar 1975, Published online: 22 Sep 2008
 

Abstract

1. Rats with biliary fistula excrete 18% of an intraperitoneal dose of [14C]imipramine (80 mg/kg) in bile within 2·5 h. Diphenylhydantoin (46 mg/kg) simultaneously administered intravenously decreases the biliary excretion of imipramine plus metabolites to 7% dose. With or without diphenylhydantoin, the highest biliary concentration of imipramine plus metabolites occurs 30-60 min after dosage.

2. With or without administration of diphenylhydantoin, 83% of the bile radioactivity is present as the conjugated 2-hydroxylated metabolites of imipramine. With imipramine alone, more conjugated 2-hydroxydesmethyl-imipramine than conjugated 2-hydroxyimipramine is excreted in the bile. Diphenylhydantoin reverses this order.

3. Administration of diphenylhydantoin does not significantly alter the concentration of imipramine plus metabolites in plasma, liver, lung and brain measured at five consecutive 30 min periods after dosage.

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