Desipramine hydroxylation: Variability and effect of antipsychotic drugs

Abstract

Steady‐state plasma concentrations of desipramine (DM1), unconjugated 2‐OH DM1, and total 2‐OH DM1 were measured in 82 depressed inpatients, 35 of whom were concurrently receiving a phenothiazine or butyrophenone antipsychotic drug. In the patients not on an antipsychotic, the ratio of unconjugated metabolite to parent varied from 0.01 to 1.5, with a median of 0.48, and was inversely related to the parent drug level. Antipsychotic drug was associated with higher DM1 levels and a lower proportion of OH‐metabolite (median, 0.23). In both groups the unconjugated form accounted for only about 10% of the total metabolite. No relationship of age, sex, drinking history, or smoking to DM1 or 2‐OH DM1 levels was found. Clinical Pharmacology and Therapeutics (1983) 33, 322–328; doi:10.1038/clpt.1983.40