title: Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia.
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.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Yagihashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Mizuno
authors.forename: Bun
authors.initials: B
authors.lastname: Chino
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.forename: Kei
authors.initials: K
authors.lastname: Sakuma
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.forename: Takahashi
authors.initials: T
authors.lastname: Takao
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000097:blood; D012044:Regression Analysis; D018967:Risperidone / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate