title: Increases in plasma concentration of m-chlorophenylpiperazine, but not trazodone, with low-dose haloperidol.
abstract: Our previous study suggested that cytochrome P4502D6 (CYP2D6) is involved in the metabolism of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). The purpose of this study was to examine the degrees of increase in plasma concentrations of trazodone and m-CPP induced by haloperidol, which is an inhibitor of CYP2D6. The subjects were nine depressed inpatients receiving trazodone at bedtime (150 mg in seven patients and 300 mg in two) for 2-19 weeks. Haloperidol at 4 mg/day was coadministered for 1 week, and blood samplings were taken before and after the coadministration. Contrary to our expectation, haloperidol did not significantly increase the mean plasma trazodone concentration (810 +/- 382 vs. 856 +/- 357 ng/ml). However, haloperidol significantly increased (p < 0.01) the mean plasma m-CPP concentration (78 +/- 31 vs. 92 +/- 34 ng/ml).
authors.affiliation: Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mihara
authors.forename: K
authors.initials: K
authors.lastname: Otani
authors.forename: M
authors.initials: M
authors.lastname: Ishida
authors.forename: N
authors.initials: N
authors.lastname: Yasui
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Ohkubo
authors.forename: T
authors.initials: T
authors.lastname: Osanai
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: K
authors.initials: K
authors.lastname: Sugawara
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood*; D014196:Trazodone / Q000097:blood* / Q000627:therapeutic use
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D010879:Piperazines; D006220:Haloperidol; C015068:1-(3-chlorophenyl)piperazine; D014196:Trazodone