Plasma Concentration of Risperidone Showed a Correlation with Daily Dose, but not with Age nor Cytochrome P‐450 2D6 Gene Polymorphisms in Japanese Schizophrenics

Abstract

Background: Risperidone, a neuroleptic, is mainly metabolized by the enzyme cytochrome P‐450 2D6 (CYP2D6), which has over 20 genetic polymorphisms, to its major active metabolite, 9‐hydroxyrisperidone (9‐OH‐risperidone). The clinical outcome in risperidone treatment is highly dependent on the plasma concentration of risperidone. Methods: In this study, in order to investigate whether individual plasma concentration of risperidone is affected by CYP2D6*4, CYP2D6*5 and major oriental mutation, CYP2D6*10A polymorphism, the genomic DNA from 53 subjects taking risperidone were analyzed by restriction fragment length polymorphism method for the determination of each genotype. Results: Neither any plasma concentration of risperidone or 9‐OH‐risperidone nor metabolic ratio of risperidone/9‐OH‐risperidone was affected by CYP2D6 genotypes. “Plasma concentration of risperidone” and “plasma concentration of 9‐OH‐risperidone” showed a strong correlation with “risperidone dose/body weight” (r=0.60, p<0.0001; r=0.54, p<0.0001, respectively). “Age” of present subjects did not show any significant correlation with plasma concentration of risperidone (r=‐0.018), 9‐OH‐risperidone (r=0.211) nor the metabolic ratio (r=‐0.237, all p>0.05). Conclusion: Based on these results that CYP2D6 genotypes and “age” showed no correlation with any plasma concentration of risperidone metabolites, it can be said that clinically the most important factor is to keep a small daily dose amount, regardless of the age of the subject. In this way, an unexpected high plasma concentration of risperidone can be avoided.