title: Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients.
abstract: We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL.
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Someya
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Shibasaki
authors.forename: T
authors.initials: T
authors.lastname: Inaba
authors.forename: S W
authors.initials: SW
authors.lastname: Cheung
authors.forename: S W
authors.initials: SW
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged
chemical_list: C040692:4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butanol; D006220:Haloperidol