Desipramine hydroxylation: variability and effect of antipsychotic drugs

Steady-state plasma concentrations of desipramine (DMI), unconjugated 2-OH DMI, and total 2-OH DMI 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 DMI 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 DMI or 2-OH DMI levels was found.