1. ¹Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
2. ²Department of Psychiatry, Dokkyo University School of Medicine, Mibucho, Tochigi, Japan
3. ³Department of Psychiatry, Shiga University of Medical Science, Otsu, Shiga, Japan
4. ⁴Saitama Kounan Hospital, Kounancho, Saitama, Japan

Correspondence: Dr T Someya, Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Niigata 951-8510, Japan. Tel: +81 25 227 2209; Fax: +81 25 227 0777; E-mail: someya@med.niigata-u.ac.jp

Received 16 August 2002; Revised 12 February 2003; Accepted 16 April 2003; Published online 4 June 2003.

Abstract

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 (1.140.69 ng/ml/mg) and RHAL (1.101.05 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=0.680.31 ng/ml/mg, RHAL=0.280.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.700.23 ng/ml/mg, RHAL=0.310.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.690.14 ng/ml/mg, RHAL=0.400.09 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 (0.430.23 ng/ml/mg, 0.340.16 ng/ml/mg) than those without CYP2D6*10 allele (0.180.16 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.