Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia  

作　　者：Zhi-ling ZHOU Xin LI Huai-yan PENG Xi-yong YU Ming YANG Feng-li SU Feng WANG Rong-hua ZHU Chun-yu DENG Qiu-xiong LIN Chuan-yue WANG Wen-biao LI Shu-guang LIN Huan-de LI 

机构地区：[1]Clinical Pharmacy Research Institute, Xiangya Second Hospital, Central South University, Changsha 410011, China [2]Research Center oJ Medical Science, Guangdong Provincial People's Hospital, Guangzhou 510080, China [3]Vascular Surgery Department, Xiangya Second Hospital, Central South University, Changsha 410011, China [4]Department of Clinical Laboratory, Third Xiangya Hospital, Central South University, Changsha 410013, China [5]Affiliated Beijing An Ding Hospital, Capital University of Medical Science, Beijing 100088, China

出　　处：《Acta Pharmacologica Sinica》2006年第3期381-386,共6页中国药理学报（英文版）

摘　　要：Aim： To study the multiple dose clinical pharmacokinetics of rispeddone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia. Methods： The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-Ⅲ （third revision of the Chinese Criteria of Mental Disorders） criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily, Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry （HPLC-MS） methods. Results： Risperidone was rapidly absorbed （Tmax was 1.6 h） and its T1/2 in plasma was short （3.2 h）. 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The Cav^ss of risperidone and 9-hydroxyrisperidone were 36.93=33,1 and 110.63=30.5 lag.h-Ll, respectively, and the AUC0-12^ss were 443.23=397.4 and 1327.23=402.3 lag·h·L^-1, respectively. CL/F and V/F of risperidone were 8.73±6.2 L,/h and 34.13±24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety. Conclusion： Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that sys- temic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.Aim： To study the multiple dose clinical pharmacokinetics of rispeddone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia. Methods： The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-Ⅲ （third revision of the Chinese Criteria of Mental Disorders） criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily, Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry （HPLC-MS） methods. Results： Risperidone was rapidly absorbed （Tmax was 1.6 h） and its T1/2 in plasma was short （3.2 h）. 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The Cav^ss of risperidone and 9-hydroxyrisperidone were 36.93=33,1 and 110.63=30.5 lag.h-Ll, respectively, and the AUC0-12^ss were 443.23=397.4 and 1327.23=402.3 lag·h·L^-1, respectively. CL/F and V/F of risperidone were 8.73±6.2 L,/h and 34.13±24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety. Conclusion： Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that sys- temic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.

关 键 词：PHARMACOKINETICS risperidone  9-hydroxyrisperidone  schizophrenia 

分 类 号：R749[医药卫生—神经病学与精神病学]