Pharmacokinetics and bioequivalence evaluation of risperidone in healthy male subjects with different CYP2D6 genotypes

The aim of this study was to evaluate the bioequivalence of risperidone in healthy male subjects representing differentCYP2D6, genotypes with respect to risperidone, 9-hydroxyrisperidone (9-OH-risperidone), and active moiety. A total of 506 Korean subjects were genotyped forCYP2D6*10 by means of allele-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Based on the genotype analysis, 24 subjects, 7 homozygous forCYP2D6*1, 10 for *10, and 7 heterozygous for *10, were recruited and received a single oral dose of 2 mg risperidone tablet in this study. Serum concentrations of risperidone and 9-OH-risperidone up to 48 h were simultaneously determined. There were no significant differences of the active moiety, risperidone, and 9-OH-risperidone between the two preparations in AUC0-α and Cmax. The 90% confidence intervals (Cls) for the ratio of means of the log-transformed AUC0-∝ and Cmax for the active moiety, risperidone, and 9-OH-risperidone were all within the bioequivalence acceptance criteria of 0.80–1.25. TheCYP2D6*10 allele particularly was associated with higher serum concentrations of risperidone and the risperidone/9-OH-risperidone ratio compared with theCYP2D6*1 allele. The results demonstrate that the two preparations of risperidone are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice. Furthermore the pharmacokinetic parameters of risperidone and the risperidone/9-OH-risperidone ratio are highly dependent on theCYP2D6 genotypes.