Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6*10/*10.

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.