title: [Involvement of cytochromeP4503A4 in the metabolism of haloperidol and bromperidol].
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Furukori
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008658:Inactivation, Metabolic; D017964:Itraconazole / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006220:Haloperidol; C006820:bromperidol