Increased plasma concentrations of bromperidol and its reduced metabolite with levomepromazine, but not with thioridazine

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks, In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with greater than or equal to 2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n = 17) significantly (p < 0.001) increased plasma concentrations of bromperidol (7.3 +/- 4.1 versus 10.2 +/- 4.8 ng/ml) and reduced bromperidol (1.8 +/- 1.4 versus 4.5 +/- 3.3 ng/ml). Thioridazine (n = 16) did not significantly change plasma concentrations of bromperidol (9.1 +/- 5.7 versus 8.6 +/- 5.5 ng/ml),while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.