Genetic Influence of CYP2D6 on Risperidone Metabolism: Pharmacokinetic and Pharmacodynamic Study in a Healthy South Indian Population.

OBJECTIVE

The CYP2D6*10 allele, which is prevalent in the Indian population, is of particular clinical significance. This study aims to investigate the effect of the CYP2D6*10 allele on the pharmacokinetics of risperidone and its metabolites following single-dose administration in healthy South Indian volunteers.

METHODS

The study was conducted with twenty healthy volunteers who were administered a single 2 mg dose of risperidone. CYP2D6 genotyping was performed using the PCR-RFLP method. Plasma levels of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OHRIS) were quantified using a UPLC-DAD system.

RESULTS

Significant differences in pharmacokinetic parameters were observed across the CYP2D6*10 genotypes. For intermediate metabolizers, the Cmax, AUC0-t, and T1/2 were approximately 1.2 times higher, and the metabolic ratio was double compared to normal metabolizers. Notably, the Cmax of the active moiety was significantly higher in intermediate metabolizers compared to normal metabolizers (p < 0.05). These findings indicate that CYP2D6 polymorphisms are associated with altered pharmacokinetic profiles of risperidone, with a reduced metabolic activation in individuals carrying the *10 allele.

CONCLUSION

The results suggest that CYP2D6 genotyping could help inform personalized dosing strategies for risperidone, though further randomized controlled trials are required to confirm these findings.