Hepatic metabolism of imipramine after prolonged administration of the drug to rats. An in vivo study.

The effect of prolonged administration of imipramine (IMI) to rats on the biliary excretion of IMI and its metabolites desipramine (DMI), 2-OH-imipramine (2-OH-IMI) and 2-OH-desipramine (2-OH-DMI) has been investigated. It was found that chronic IMI decreased the ratio DMI/IMI and 2-OH-IMI/IMI excreted with the bile and increased the ratio 2-OH-DMI/DMI. This was observed for 3 h after the last dose of chronic IMI, and suggested an inhibition of IMI demethylation and hydroxylation, and acceleration of DMI hydroxylation. 6 h after the dose of IMI the biliary ratio DMI/IMI and 2-OH-IMI/IMI increased and this might indicate an acceleration of IMI metabolism at later time intervals after IMI administration.