Effect of the cytochrome P450 2D6*10 allele on risperidone metabolism in Japanese psychiatric patients.

OBJECTIVE

The sum of the serum levels of risperidone (RIS) and 9-hydroxyrisperidone (9-OH-RIS), which is the active moiety serum level, could be important for estimating the clinical effects of RIS. However, there have been no consistent results reported about the relationship between cytochrome P450 (CYP) 2D610 allele and plasma 9-OH-RIS or active moiety levels. We investigated the effect of the number of CYP2D610 alleles on steady-state plasma RIS, 9-OH-RIS, and active moiety levels in Japanese patients.

METHODS

Steady-state plasma RIS, 9-OH-RIS, and active moiety levels were measured in 64 patients treated with an average dosage of 4.6 mg/day.

RESULTS

The number of CYP2D610 alleles significantly affected dose-corrected plasma RIS levels (p = 0.001), and the median concentrations in ng/ml/mg were 0.94 (0 allele) vs. 1.73 (1 allele) vs. 3.05 (2 alleles). The number of CYP2D610 alleles did not affect plasma 9-OH-RIS or active moiety levels.

CONCLUSION

The present study shows that the number of CYP2D610 alleles affected plasma RIS levels but not plasma 9-OH-RIS and plasma active moiety levels. Because the plasma active moiety levels can influence antipsychotic effects or side effects, the genetic screening of the CYP2D610 allele for RIS in Asian populations may not be clinically important.