AbstractObjectiveRisperidone is converted to 9‐hydroxyrisperidone by CYP2D6. Two parameters were used to examine the influences of CYP2D6 polymorphism and of co‐medication on risperidone metabolism: the risperidone:9‐hydroxyrisperidone concentration ratio (R:9‐OHR ratio) and the sum of the risperidone and 9‐hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East Asians.MethodsGenotyping using the P450 microarray system was performed for 89 Japanese patients with schizophrenia receiving risperidone. The patients with CYP2D6*1/*1, *1/*2, or *2/*2 were classified as Group 1, those with one CYP2D6*10 allele (CYP2D6*1/*10 or *2/*10) were classified as Group 2, and those with two CYP2D6*10 alleles were classified as Group 3. The R:9‐OHR and C:D ratios were analyzed using two‐way ANOVAs with the CYP2D6 genotype and co‐medication with CYP2D6‐dependent drugs as independent variables.ResultsBoth the “genotype” and the “co‐medication” factors had significant impacts on the R:9‐OHR ratio (p = 0.011,p < 0.001). The “genotype” factor also had a significant impact on the C:D ratio (p = 0.032). However, the “co‐medication” factor did not have a significant impact on the C:D ratio (p = 0.129).ConclusionsThe CYP2D6*10 polymorphism and the presence of co‐medication exerted significant influences on the pharmacokinetics of risperidone. Copyright © 2009 John Wiley & Sons, Ltd.