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

Tatsuhiko Yagihashi, Masafumi Mizuno, Bun Chino, Yuji Sato, Kei Sakuma, Toru Takebayashi, Takao Takahashi, Kenjiro Kosaki

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 CYP2D6a10 allele (CYP2D6*1/2,10 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.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalHuman Psychopharmacology
Volume24
Issue number4
DOIs
Publication statusPublished - 2009

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Cytochrome P-450 CYP2D6
Risperidone
Schizophrenia
Alleles
Pharmaceutical Preparations
Genotype
Analysis of Variance
Pharmacokinetics

Keywords

  • CYP2D6
  • Pharmacogenetics
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Pharmacology (medical)

Cite this

Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patientswith schizophrenia. / Yagihashi, Tatsuhiko; Mizuno, Masafumi; Chino, Bun; Sato, Yuji; Sakuma, Kei; Takebayashi, Toru; Takahashi, Takao; Kosaki, Kenjiro.

In: Human Psychopharmacology, Vol. 24, No. 4, 2009, p. 301-308.

Research output: Contribution to journalArticle

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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 CYP2D6a10 allele (CYP2D6*1/2,10 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.",
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T1 - Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patientswith schizophrenia

AU - Yagihashi, Tatsuhiko

AU - Mizuno, Masafumi

AU - Chino, Bun

AU - Sato, Yuji

AU - Sakuma, Kei

AU - Takebayashi, Toru

AU - Takahashi, Takao

AU - Kosaki, Kenjiro

PY - 2009

Y1 - 2009

N2 - 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 CYP2D6a10 allele (CYP2D6*1/2,10 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.

AB - 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 CYP2D6a10 allele (CYP2D6*1/2,10 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.

KW - CYP2D6

KW - Pharmacogenetics

KW - Risperidone

KW - Schizophrenia

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