Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia.
BACKGROUND
The CYP2D6*10 (*10) allele that causes decreased CYP2D6 activity is present in Asians with a high frequency of about 50%. In this study we studied the effects of the *10 allele on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol.


METHODS
The subjects were 67 Japanese inpatients with schizophrenia who had only the wild-type or *10 alleles. Thirty-four patients were homozygous for the wild-type allele, and 26 were heterozygous and 7 were homozygous for the *10 allele. All patients had been receiving 12 mg/day haloperidol for at least 2 weeks. Plasma concentrations of haloperidol and reduced haloperidol were measured by HPLC.


RESULTS
The mean +/- SD values of haloperidol Css in the patients with 0, 1, and 2 *10 alleles were 22.8+/-11.0, 30.1+/-10.6, and 31.2+/-21.2 nmol/L, respectively, and those values for reduced haloperidol were 6.1+/-2.9, 9.5+/-3.7, and 9.9+/-6.2 nmol/L, respectively. The mean haloperidol Css was significantly (P < .05) higher in the patients with 1 *10 allele than in those with no *10 alleles. The mean Css of reduced haloperidol was significantly (P < .05) higher in the patients with 1 and 2 *10 alleles than in those with no *10 alleles.


CONCLUSIONS
This study suggests that the *10 allele plays an important role in controlling the Css of both haloperidol and reduced haloperidol, especially in Asian subjects.
Mihara
K
K
Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
Suzuki
A
A
Kondo
T
T
Yasui
N
N
Furukori
H
H
Nagashima
U
U
Otani
K
K
Kaneko
S
S
Inoue
Y
Y
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007564:Japan; D008297:Male; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol