Imipramine Disposition in Alcoholics

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Abstract
The disposition of orally administered imipramine (IMI) was studied in 11 depressed alcoholic and 12 depressed nonalcoholic male inpatients. Subjects received 50 mg three times daily for at least 10 days to ensure steady state. Following a temporary discontinuation of therapy, several blood samples were drawn over a 40-hour period. Imipramine, desipramine, and their 2-hydroxylated metabolites were measured in plasma using a high performance liquid chromatography assay. Eight hours following the last dose, alcoholics had significantly lower IMI (50 ± 41 versus 106 ± 46 ng/ml; ppp<0.005) over the clearance found in control subjects. The latter seems a more likely result of chronic ethanol intake. The fact that lower levels of IMI in the alcoholic group were accompanied by a lack of efficacy in relieving depressive symptomatology suggests that whether through an effect on bioavailability or intrinsic clearance, ethanol consumption is an important consideration when recommending tricyclic therapy.

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