阿立哌唑片在中国健康人体的单剂和多剂药动学研究  

Pharmacokinetics of aripiprazole after single and multiple dosing in Chinese healthy subjects

作　　者：王洪允[1] 沈凯[1] 江骥[1] 胡蓓[1] 

机构地区：[1]中国医学科学院北京协和医院临床药理中心,北京100730

出　　处：《中国新药杂志》2013年第7期814-818,841,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2008ZX09312-016)

摘　　要：目的:研究阿立哌唑片在健康人体的药动学。方法:采用开放、平行试验设计,44名中国健康志愿者分别单次或多次口服阿立哌唑片。采用LC-MS/MS测定阿立哌唑及代谢物脱氢阿立哌唑的血药浓度,以WinNolin按照非房室模型计算药动学参数。结果:在10～30 mg剂量范围内,AUC0～t和Cmax均与剂量呈线性比例关系。连续服药14 d(10 mg.d-1)后,阿立哌唑在体内达到稳态,并出现明显蓄积。安全性评价结果显示,不良反应多为轻度或暂时性的,并与剂量无关。结论:在10～30 mg剂量范围内,阿立哌唑在中国人体内呈线性药动学特征,多次服药后在体内有明显蓄积,该药在中国健康受试者体内耐受良好。Objective： To evaluate the pharmacokinetics of aripiprazole in healthy subjects. Methods： In an open-label and parallel group study, 44 healthy Chinese subjects received single or multiple-dose of aripiprazole tablet（s）. Plasma concentrations of aripiprazole and its metabolite dehydroaripiprazole were determined by LC-MS/ MS. Pharmacokinetie parameters were calculated with WinNolin software using non-compartment analysis. Results： AUC0-1, and Cmax were increased proportionally as dose escalation among the range of 10 to 30 rag. The steady state of aripiprazole was attained by d 14 after 10 mg qd for 14 d and serious accumulation was observed. Adverse events happened in the study were generally mild, transient, and independent on dose. Conclusion： Dose proportionality of aripiprazole is concluded over the range of 10 to 30 rag. Aripiprazole has been found to be obviously accumulated after multiple administrations and well tolerated in healthy Chinese subjects.

关 键 词：阿立哌唑 药动学 精神分裂症 非典型抗精神病药物 中国健康受试者 

分 类 号：R971[医药卫生—药品]