Furukori H
Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1998 Feb;18(1):9-14.
To clarify the involvement of cytochromeP450 (CYP) 3A4 in the metabolism of haloperidol and bromperidol in humans, the effects of itraconazole, a potent inhibitor of CYP3A4, on steady-state plasma concentrations of both drugs and their reduced metabolites were investigated using 21 schizophrenic patients. Patients treated with haloperidol 12 or 24 mg/day (n = 13) or bromperidol 12 or 24 mg/day (n = 8) for at least 2 weeks were then given itraconazole 200 mg/day for 7 days. Blood samplings were performed before administration, 1 week during itraconazole coadministration and 1 week after its discontinuation together with clinical assessments. Plasma concentrations of haloperidol and bromperidol and their reduced metabolites were significantly higher during itraconazole treatment (P < 0.01). Deterioration in the neurological side effects of haloperidol was observed during itraconazole coadministration. Thus, this study suggests that itraconazole inhibits the metabolism of haloperidol and bromperidol, and that CYP3A4 is involved in the metabolism of both drugs.
