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Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia

✍ Scribed by Tatsuhiko Yagihashi; Masafumi Mizuno; Bun Chino; Yuji Sato; Kei Sakuma; Toru Takebayashi; Takahashi Takao; Kenjiro Kosaki

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
121 KB
Volume
24
Category
Article
ISSN
0885-6222

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✦ Synopsis

Abstract

Objective

Risperidone 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.

Methods

Genotyping 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.

Results

Both 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).

Conclusions

The CYP2D6*10 polymorphism and the presence of co‐medication exerted significant influences on the pharmacokinetics of risperidone. Copyright © 2009 John Wiley & Sons, Ltd.

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