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 activit y 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 concentra tions (C-ss) of haloperidol and reduced haloperidol. Methods: The subjects were 67 Japanese inpatients with schizophrenia who ha d only the wild-type or *10 alleles, Thirty-four patients were homozygous f or 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 haloperi dol were measured by HPLC. Results: The mean +/- SD values of haloperidol C-ss 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 haloperid ol C-ss was significantly (P <.05) higher in the patients with 1 *10 allele than in those with no *10 alleles, The mean C-ss of reduced haloperidol wa s significantly (P <.05) higher in the patients with 1 and 2 *10 alleles th an in those with no *10 alleles, Conclusion: This study suggests that the *10 allele plays an important role in controlling the C-ss of both haloperidol and reduced haloperidol, espec ially in Asian subjects.