阿折地平片的人体药动学研究

 目的建立人血浆中阿折地平的HPLC-MS测定方法,并对其人体药动学进行评价。方法12名健康受试者分别po单剂量阿折地平片8,16 mg,受试者经清洗期后,连续po阿折地平8 mg,每日1次,连续服药8 d。采用HPLC-MS测定人血浆中阿折地平浓度,并计算单次及多次给药后的药动学参数。结果单次口服阿折地平片8及16 mg后,阿折地平的消除半衰期分别为(25.0±4.3)和(24.6±5.6)h,达峰时间分别为(2.9±1.4)和(2.6±0.8)h;达峰浓度分别为(5.13±2.20)和(9.48±3.70)μg·L^-1;AUC分别为(53.6±17.1)和(107.9±39.1)μg·h·L^-1。多次po阿折地平片8 mg后,阿折地平的消除半衰期为(25.2±5.0)h,达峰时间为(3.1±1.1)h,达峰浓度为(6.12±2.27)μg·L^-1,AUC为(53.6±18.4)μg·h·L^-1.结论本试验建立的测定方法灵敏、准确、简便。阿折地平在8～16 mg内呈线性药动学特征,多剂量给药与单剂量给药药动学参数基本一致。

Study on Pharmacokinetics of Azelnidipine in Healthy Volunteers

OBJECTIVE To study the phannacokinetics of azelnidipine in 12 healthy Chinese volunteers after the single and multiple dose administrations.METHODS Twelve volunteers received a single dose of 8 and 16 mg azelnidipine respectively.After wash out period,the volunteers received 8 mg azelnidipine once a day for eight consecutive days.The azelnidipine concentration in plasma was determined by HPLC-MS and the pharmacokinetic parameters were calculated.RESULTS The pharmacokinetic parameters after the single dose of 8 and 16 mg were:t_1/2(25.0±4.3)and (24.6±5.6 h,t_max(2.9±1.4)and(2.6±0.8)h ,ρ_max (5.13±2.20) and (9.48±3.70)μg·L^-1,AUC(53.6±17.1) and(107.9±39.1)μg·h·L^-1,respectively.The pharmacokinetic parameters after multi-dose of 8 mg azelnidipine were:t_1/2(25.2±5.0) h,t_max(3.1±1.1) h,ρ_max(6.12±2.27)μg·L^-1and AUC(53.6±18.4)μg·h·L^-1.CONCLUSION The method was simple and accurate.A linear pharmacokinetic profile was proved in the range of 8～16 mg dose.There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.