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.