Effects of CYP2D6and CYP3A5Genotypes on the Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Korean Schizophrenic Patients

This study was conducted to evaluate the effects of the CYP2D6and CYP3A5genotypes on the steady-state plasma levels of risperidone (RIS), 9-hydroxyrisperidone (9-OH-RIS), and the active moiety (RIS plus 9-OH-RIS) in Korean schizophrenic patients. Sixty-four Korean schizophrenic patients were enrolled. CYP2D6and CYP3A5genotypes were determined, and the plasma levels of RIS and 9-OH-RIS were measured using high-performance liquid chromatography. The dose-normalized plasma concentrations of RIS, 9-OH-RIS, and the active moiety were compared according to the CYP2D6and CYP3A5genotypes. Among the patients, 57 were CYP2D6extensive metabolizers (EMs; CYP2D61/1, 1/10, and 10/10) and 7 were CYP2D6poor metabolizers (PMs; CYP2D61/5and 10/5). For the CYP3A5genotype, 30 patients were CYP3A51expressors (1/1n = 1 and 1/3n = 29) and 34 patients were CYP3A5nonexpressors (3/3). The plasma levels of RIS (2.03 ng/mL per milligram for EMs vs 5.57 ng/mL per milligram for PMs, P< 0.001) and 9-OH-RIS (5.06 ng/mL per milligram for EMs vs 0.22 ng/mL per milligram for PMs, P< 0.001) were significantly different among CYP2D6genotype groups, but the CYP2D6EMs (7.09 ng/mL per milligram) and PMs (5.79 ng/mL per milligram) did not show no difference in the levels of the active moiety (P= 0.470). CYP3A5nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5nonexpressors exhibited significantly higher concentrations than CYP3A5expressors (5.42 vs 3.51 ng/mL per milligram, P= 0.022). In addition, concentrations of the active moiety were also significantly different between the CYP3A5nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P= 0.005). In conclusion, both CYP2D6and CYP3A5genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5genotype but not by the CYP2D6genotype.