Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.
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.
Someya
Toshiyuki
T
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
Shimoda
Kazutaka
K
Suzuki
Yutaro
Y
Sato
Satoshi
S
Kawashima
Yoshiaki
Y
Hirokane
Genta
G
Morita
Sachiyo
S
Yokono
Aya
A
Takahashi
Saburo
S
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
D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol