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Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with
Hee-Doo Yoo1, Sang-No Lee, Hyun-Ah Kang
1College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Korea.
Background And Purpose:
The objective of this study was to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics.
Experimental Approach:
Seventy-two healthy Korean volunteers receiving a single oral dose of 2 mg risperidone were included in this study.
Key Results:
Significant differences were observed between the ABCB1 3435C>T genotypes for the pharmacokinetic parameters (peak serum concentration) of risperidone and the active moiety (risperidone and its main metabolite, 9-hydroxyrisperidone). There were no significant differences in the area under the serum concentration-time curves of risperidone and the active moiety among the ABCB1 2677G>T/A and 3435C>T genotypes. However, the peak serum concentration and area under the serum concentration-time curves were significantly different among the ABCB1 3435C>T genotypes in CYP2D6*10/*10.
Conclusions And Implications:
These findings indicate that polymorphisms of ABCB1 3435C>T in individuals with CYP2D6*10/*10, which has low metabolic activity, could play an important role in the potential adverse effects or toxicity of risperidone.
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