健康人单次和多次口服阿立哌唑片的药动学研究

 目的建立测定阿立哌唑血浆药物浓度的HPLC-UV检测法,研究国产阿立哌唑片在人体的药动学。方法12名健康志愿受试者和14名健康志愿受试者分别单剂量和多剂量po 20 mg国产阿立哌唑片,采用HPLC测定给药后不同时间点血浆中阿立哌唑浓度,用DAS1.0(3P97药动学程序Windows升级版)处理经时血药浓度数据,计算主要药动学参数。结果单次口服阿立哌唑片后的主要药动学参数:ρ_max为(108.4±22.5)μg·L^-1,t_max为(4.9±0.7)h,AUC_{0～192 h}为(5 748.2±874.5)μg·h·L^-1,t_1/2β为(107.43±29.03)h,CL/F和V/F分别为(3.56±0.55)L·h^-1和(261.60±49.14)L。多次口服阿立哌唑片共14 d达稳态,稳态血药浓度期间给药后(4.0±0.9)h达到峰浓度(480.3±126.2)μg·L^-1,AUC_{0～360 h}为(38 166.6±13 241.2)μg·h·L^-1,t_1/2β为(91.0±21.1)h,CL/F和V/F分别为(0.62±0.36)L·h^-1和(60.9±43.7)L。结论国产阿立哌唑的血药浓度-时间曲线符合二室开放模型,为今后的合理用药打下基础。

Study on Pharmacokinetics of Domestic Aripiprazole After Single and Multiple Dosing in Healthy Volunteers

OBJECTIVE To develop a HPLC-UV method for determining Aripiprazole in human plasma and study the pharmacokinetic profiles of domestic Aripiprazole tablets in healthy volunteers.METHODS A single and multiple oral doses of domestic aripiprazole were given to 12 and 14 healthy volunteers respectively.Aripiprazole concentrations in plasma were determined by HPLC method.The pharmacokinetic parameters of aripiprazole were obtained with statistical analysis by DAS1.0.RESULTS The main pharmacokinetic parameters of a single dose of aripiprazole were as followed:ρ_max was (108.4±22.5) μg·L^-1,t_max was(4.9±0.7) h,AUC_{0～192 h} was(5 748.2±874.5) μg·h·L^-1,t_1/2βwas(107.4±29.0)h,CL/F was(3.56±0.55) L·h^-1 and V/F was(261.6±49.1) L.In multiple dose study,aripiprazole were given to the healthy volunteers for 14 d to achieve steady state,the peak concentration of(480.3±126.2) μg·L^-1 and was reached at(4.0±0.9) h after the last administration in steady state.AUC_{0～360 h} was(38 166.6±13 241.2) μg·h·L^-1,t_1/2β was(91.0±21.1)h,CL/F was(0.62±0.36) L·h^-1 and V/F was(60.9±43.7) L.CONCLUSION The concentration-time curves of aripiprazole were described by a two-compartment open model.And it offered necessary information for clinical use of aripiprazole in Chinese.