Mihara Kazuo, Kondo Tsuyoshi, Yasui-Furukori Norio, Suzuki Akihito, Ishida Masayuki, Ono Shingo, Kubota Takahiro, Iga Tatsuji, Takarada Yutaka, de Vries Ronald, Kaneko Sunao
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan.
Ther Drug Monit. 2003 Jun;25(3):287-93. doi: 10.1097/00007691-200306000-00006.
The effects of various CYP2D6 genotypes on the steady-state plasma concentrations (Css) of risperidone and its active metabolite, 9-hydroxyrisperidone, were studied in 85 Japanese schizophrenic patients (27 men and 58 women) treated with 6 mg/d risperidone for at least 2 weeks. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using liquid chromatography-tandem mass spectrometry. The patients had the following CYP2D6 genotypes: wild-type (wt)/wt (40 patients), CYP2D6*10 (10)/wt ( 28), CYP2D65 (*5)/wt ( 8), *10/*10 ( 5), 5/10 ( 3), and CYP2D64/CYP2D614 ( 1), respectively. The Css values of risperidone and 9-hydroxyrisperidone were corrected to the median body weight of 58 kg. The medians (ranges) of the Css of risperidone in the aforementioned genotype groups were 2.2 (0.37-35.7), 6.4 (2.1-26.5), 12.3 (4.7-39.5), 19.4 (13.4-26.4), 64.0 (41.6-68.8), and 91.8 nmol/L. Those values for risperidone-to-9-hydroxyrisperidone ratio were 0.03 (0.01-0.33), 0.06 (0.03-0.19), 0.14 (0.07-0.29), 0.28 (0.25-0.38), 0.48 (0.38-0.58), and 2.35, respectively. The Css of risperidone was significantly (P < 0.05 or P < 0.001) different among the four genotype groups (wt/wt, *10/wt, *5/wt, and *10/*10), except between the *5/wt and *10/*10 groups. Also, the risperidone-to-9-hydroxyrisperidone ratio significantly (P < 0.005 or P < 0.001) differed among these genotype groups. No significant differences were found in the Css of 9-hydroxyrisperidone and the active moiety (the Css of risperidone plus 9-hydroxyrisperidone) among these genotype groups. This study confirms previous findings that the CYP2D6 status affects the Css of risperidone via its strong regulation of 9-hydroxylation of risperidone. However, similar active moiety of risperidone among different genotype groups suggests that the determination of the CYP2D6 genotype has little importance for clinical situations.
在85例接受6mg/d利培酮治疗至少2周的日本精神分裂症患者（27例男性和58例女性）中，研究了各种CYP2D6基因型对利培酮及其活性代谢物9-羟基利培酮稳态血药浓度（Css）的影响。采用液相色谱-串联质谱法测定利培酮和9-羟基利培酮的血药浓度。患者的CYP2D6基因型分别为：野生型（wt）/wt（40例）、CYP2D6*10（10）/wt（28例）、CYP2D65（*5）/wt（8例）、*10/*10（5例）、5/10（3例）和CYP2D64/CYP2D614（1例）。利培酮和9-羟基利培酮的Css值校正为中位数体重58kg。上述基因型组中利培酮Css的中位数（范围）分别为2.2（0.37 - 35.7）、6.4（2.
