培哚普利两剂型的药动学及人体生物等效性研究

Pharmacokinetics and Bioequivalence Study of Two Perindopril Preparations for Multiple Cross-Over Design in Healthy Volunteers

目的研究18名健康志愿者单剂量口服3种培哚普利制剂后血药浓度经时过程,及体内的药动学特征和生物等效性。方法采用三交叉试验方法进行试验设计,18名健康志愿者随机分为3组,交叉口服单剂量培哚普利片(T1)、培哚普利胶囊(T2)、培哚普利片(R),HPLC-MS/MS测定血中药物浓度,以BAPP2.2计算其药动学参数,评价3制剂的生物等效性。结果口服3种培哚普利制剂4mg后主要药动学参数ρmax分别为(58.63±16.47),(63.83±17.45)和(63.87±17.99)μg·L-1;tmax分别为(0.67±0.24),(0.58±0.19)和(0.66±0.25)h;t1/2分别为(0.72±0.21),(0.75±0.19)和(0.74±0.18)h;MRT分别为(1.28±0.12),(1.25±0.30)和(1.27±0.19)h;AUC0-t分别为(70.70±13.58),(69.99±13.07),(70.31±14.45)μg·h·L-1;AUC0-∞分别为(71.43±13.81),(70.81±13.18),(71.01±14.60)μg·h·L-1。主要药动学参数经统计学分析,无显著差异。结论2种受试制剂与参比制剂在健康志愿者体内的药动学参数相似,具有生物等效性。

OBJECTIVE To observe the concentration-time process of perindopril in 18 healthy volunteers and evaluate the bioequivalence of the three kinds of perindopril preparations. METHODS Eighteen healthy human volunteers were divided randomly into three groups, and a single oral dose of 4 mg reference and test perindopril preparations were given to 18 healthy volunteers in a 3-way cross-over study. Plasma concentrations were determined by HPLC-MS/MS method. RESULTS The main pharmacokinetic parameters calculated by BAPP2.2 software were as follows： Pmax （58.63 ± 16.47）, （63.83 ± 17.45） and （63.87± 17.99）μg·h·L^-1 tmx（0.67±0.24）, （0.58±0.19）, and （0.66±0.25） h; t1/2 （0.72±0.21）, （0.75±0.19） and （0.74±0.18）hi MRT （1.28±0.12）, （1.25±0.30） and（1.27±0.19）h;AUC0-t （70.70±13.58）, （69.99±13.07） and （70.31±14.45）±μg·h·L^-1;AUC0-∞ （71.43±13.81）, （70.81±13.18） and （71.01±14.60） μg·h·L^-1, respectively. CONCLUSION 3 preparations are bioequivalent.