Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients.

This study was conducted to evaluate the effects of the CYP2D6 and CYP3A5 genotypes 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. CYP2D6 and CYP3A5 genotypes 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 CYP2D6 and CYP3A5 genotypes. Among the patients, 57 were CYP2D6 extensive metabolizers (EMs; CYP2D6*1/*1, *1/*10, and *10/*10) and 7 were CYP2D6 poor metabolizers (PMs; CYP2D6*1/*5 and *10/*5). For the CYP3A5 genotype, 30 patients were CYP3A5*1 expressors (*1/*1 [n = 1] and *1/*3 [n = 29]) and 34 patients were CYP3A5 nonexpressors (*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 CYP2D6 genotype groups, but the CYP2D6 EMs (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). CYP3A5 nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5 nonexpressors exhibited significantly higher concentrations than CYP3A5 expressors (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 CYP3A5 nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P = 0.005). In conclusion, both CYP2D6 and CYP3A5 genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5 genotype but not by the CYP2D6 genotype.

A study of the reliability and validity of the korean version of the penn alcohol craving scale for alcohol-dependent patients.

OBJECTIVE: The Penn Alcohol Craving Scale (PACS) is a stronger predictor of subsequent drinking and relapse of alcohol dependence that can be administered more quickly and easily than other craving scales. The goal of this study was to develop the Korean version of the Penn Alcohol Craving Scale (PACS-K). METHODS: To examine the psychometric properties of the PACS-K, responses were chosen from 80 patients admitted to a treatment facility for alcohol dependence. RESULTS: The PACS-K possesses good psychometric properties, as assessed by Cronbach's alpha estimates (Cronbach's alpha=0.91). The test-retest reliability of the PACS-K showed high correlation (p<0.01) when the retest interval was 1 day. When the validity of the PACS-K was investigated using correlation analysis with two other craving scales (the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analogue Scale (VAS), high correlations were obtained between total PACS scores and total OCDS scores, and between total PACS scores and VAS scores (p<0.01, respectively). CONCLUSION: The PACS-K is a reliable and valid measure of alcohol cravings, and it could be useful for predicting which individuals are at risk for subsequent relapse.