不同剂量阿折地平在中国健康人体内的药代动力学

Pharmacokinetics of different dosages of azelnidipine in healthy volunteers

目的研究阿折地平(抗高血压药)在健康人体的药代动力学。方法 24名健康受试者分为3组,单次口服高、低(16,8 mg)2个剂量组和多次口服剂量组(每天服药1次,每次8 mg,连续服药7 d)。用液相串联质谱法测定血浆中阿折地平的血药浓度变化,药代动力学参数以SPSS 13.0软件求算。结果阿折地平高、低剂量组及多次给药组的代谢参数如下:Cmax分别为(10.61±3.93),(5.91±2.83)和(5.88±1.90)μg.L-1;Tmax分别为(3.67±0.99),(3.33±1.30)和(3.17±0.72)h;t1/2分别为(28.00±7.72),(20.34±7.60)和(28.17±7.93)h;AUC0-t分别为(139.50±72.90),(61.17±33.78)和(86.72±41.59)μg.h.L-1。多次给药的稳态AUCss(55.54±18.78)μg.h.L-1。健康受试者口服阿折地平片8,16 mg后,主要药代动力学参数除t1/2外,AUC0-t/D、AUC0-∞/D、Cmax/D在2个剂量组间均无统计学差异。多次给药t1/2与单次给药t1/2相比有所升高,CLz/F略有下降,具有统计学意义(P<0.05)。结论阿折地平在中国健康人体内在8～16 mg内呈线性药代动力学特征;本品每天给药1次,在中国人体内几无蓄积作用。

Objective To study the pharmacokinetics of different dosages of azelnidipine in Chinese healthy volunteers.Methods Twenty-four healthy volunteers were devided into three groups.The volunteers in the three groups received single dose of 16 mg azelnidipine,single dose of 8 mg azelnidipine and multiple dosing of 8 mg azelnidipine by oral administration（8 mg per day,7 days continuous）,respectively.Concentrations of azelnidipine in plasma were determined by HPLC/MS/MS.The pharmacokinetics parameters were calculated by SPSS 13.0 software.Results The main pharmacokinetic parameters of the three groups were as follows： Cmax were（10.61±3.93）,（5.91±2.83） and（5.88±1.90） μg·L-1;Tmax were（3.67±0.99）,（3.33±1.30） and（3.17±0.72） h;t1/2 were（28.00±7.72）,（20.34±7.60） and（28.17±7.93）h;AUC0-t were（139.50±72.90）,（61.17±33.78）and（86.72±41.59） μg·h·L-1.respectively.The steady-state AUCss for multiple was（55.54±18.78） μg·h·L-1.The main pharmacokinetics parameters had no significant difference in AUC0-t /D,AUC0-∞/D,Cmax/D except t1/2.The half-time of multiple dosing was longer than that of single dose and there was a decline in the values of CLz/F,which had statistical difference（P0.05）.Conclusion Pharmacokinetic characteristics of azelnidipine in Chinese healthy volunteers showed a linear relationship,within the dose range of 8-16 mg;Azelnidipine with administration of a single oral dose daily had almost no accumulation effect in Chinese.