Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia.
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.
Yagihashi
Tatsuhiko
T
Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Mizuno
Masafumi
M
Chino
Bun
B
Sato
Yuji
Y
Sakuma
Kei
K
Takebayashi
Toru
T
Takao
Takahashi
T
Kosaki
Kenjiro
K
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*
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate