The effect of prolonged administration of imipramine (IMI) (20 mg/kg/day po) to rats on IMI metabolism by liver microsomes was investigated. It was found that chronic treatment of rats with IMI decreased IMI and desipramine (DMI) hydroxylase activity while IMI demethylase activity was only slightly diminished. Kinetic study of IMI hydroxylation and N-demethylation (carried out in the presence or absence of DMI) indicated that DMI inhibited competitively IMI metabolism. These results suggest that the increase of IMI and DMI levels in the blood plasma of rats treated chronically with IMI may be due, at least partially, to the inhibition of IMI and DMI biotransformation in the liver.
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