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 CYP2D65 allele (CYP2D61/CYP2D65, CYP2D65/CYP2D610) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D65 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 CYP2D65 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D610 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D610 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D610 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 CYP2D610 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D610 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 CYP2D610 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D610 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D610 allele with CYP2D65 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.