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Mihara, K. et al.

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. CONCLUSION: 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.[1]

References

Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia. Mihara, K., Suzuki, A., Kondo, T., Yasui, N., Furukori, H., Nagashima, U., Otani, K., Kaneko, S., Inoue, Y. Clin. Pharmacol. Ther. (1999) [Pubmed]

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