阿折地平片的人体药动学研究

Study on Pharmacokinetics of Azelnidipine in Healthy Volunteers

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。

OBJECTIVE To study the pharmacokinetics of azclnidipine 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 pharmacokinetie parameters were calculated. RESULTS The pharmaeokinetie, parameters after the single dose of 8 and 16 mg were：t1/2 （25.0±4. 3） and （24. 6±5.6） h,tmax （2. 9±1.4） and （2.6±0. 8） h,ρmax （5.13±2.20） and （9.48±3.70） μg·L^-1,AUC（53.6±17.1） and （107.9±39.1） μg·h^-1·L^-1, respectively. The pharmacokinetic parameters after multi-dose of 8 mg azelnidipine were： t1/2 （25.2±5.0） h,tmax （3. 1±1. 1） h ,ρmax（6. 12 ±2.27 ） μg·L^-1 and AUC（53.6±18.4） μg·h^-1·L^-1. CONCLUSION The method was simple and accurate, A linear pharmacokinetic profile was proved in the range of 8 - 16 mg close, There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.