title: Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.
abstract: We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Niigata 951-8510, Japan. someya@med.niigata-u.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sato
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Genta
authors.initials: G
authors.lastname: Hirokane
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Morita
authors.forename: Aya
authors.initials: A
authors.lastname: Yokono
authors.forename: Saburo
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged
chemical_list: D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol