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

Hum Psychopharmacol. 2009 Jun;24(4):301-8. doi: 10.1002/hup.1025.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / pharmacokinetics*
  • Cytochrome P-450 CYP2D6 / classification
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Humans
  • Isoxazoles / blood
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Paliperidone Palmitate
  • Psychiatric Status Rating Scales
  • Pyrimidines / blood
  • Regression Analysis
  • Risperidone / pharmacokinetics*
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism*

Substances

  • Antipsychotic Agents
  • Isoxazoles
  • Pyrimidines
  • Cytochrome P-450 CYP2D6
  • Risperidone
  • Paliperidone Palmitate