Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety

• Published in: Journal of clinical pharmacology Vol. 50; no. 6; p. 659
• Main Authors: Xiang, Qian, Zhao, Xia, Zhou, Ying, Duan, Jing Li, Cui, Yi Min
• Format: Journal Article
• Language: English
• Published: England 01.06.2010
• Subjects: Adult; Alleles; Antipsychotic Agents - pharmacokinetics; Area Under Curve; Asian Continental Ancestry Group - genetics; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP3A - genetics; Genotype; Humans; Isoxazoles - pharmacokinetics; Male; Paliperidone Palmitate; Polymorphism, Genetic; Pyrimidines - pharmacokinetics; Risperidone - pharmacokinetics
• ISSN: 1552-4604
• DOI: 10.1177/0091270009347867

Clinical studies suggest that plasma levels of risperidone and its active moiety (risperidone + 9-hydroxyrisperidone) correlate with adverse drug effects. The aim of this study is to evaluate the pharmacogenetic variability in the disposition of risperidone and the active moiety in healthy Chinese subjects. A 2-mg single dose of risperidone is orally administered to 23 healthy Chinese subjects. The risperidone and 9-hydroxyrisperidone serum concentrations are measured. The polymorphic alleles of CYP2D6*10, CYP3A5*3, MDR1 C1236T, G2677T/A, and C3435T are determined in each subject. The mean maximum plasma concentration and area under the time-concentration curve extrapolated to infinity for risperidone are significantly higher in subjects possessing the CYP2D6*10 allele than in those with the CYP2D6*1/*1 and *1/*10 genotype. For active moiety, the subjects who carry both homozygous CYP2D6*10 and homozygous CYP3A5*3 have 98% higher area under the time-concentration curve extrapolated to infinity and 59% higher maximum plasma concentration compared with other CYP2D6 EM subjects. The MDR1 2677GA genotype may also play a role in risperidone pharmacokinetics. Further studies are needed to explore the impact of MDR1 2677GA and CYP3A5 polymorphisms on risperidone therapy.