高原世居藏族健康人中苯磺酸氨氯地平的药代动力学特征研究

Study on pharmacokinetic characteristics of amlodipine besylate among Tibetan healthy human body living in plateau

目的探究高原世居藏族健康人中苯磺酸氨氯地平的药代动力学特征。方法招募8名高原世居藏族健康受试者,给予口服单剂量苯磺酸氨氯地平5 mg,给药前0 h和给药后1、2、4、8、24、48、72 h采集外周静脉血,采用高效液相色谱-质谱/质谱联用法测定血浆苯磺酸氨氯地平浓度,采用Drug And Statistics 3.0软件计算药代动力学参数。结果8名藏族健康受试者单次口服5 mg苯磺酸氨氯地平的平均药代动力学参数如下:达峰时间为(4.4±2.5)h,最大血药浓度为(3.1±0.5)μg/L,半衰期为(40±13)h,0~72 h和0~∞h时的血浆药物浓度-时间曲线下面积分别为(115±11)μg·h/L和(159±16)μg·h/L。结论苯磺酸氨氯地平在高原地区的平均达峰时间可能与高原环境对消化系统的影响有关,高原环境造成胃肠黏膜屏障的改变、损伤等可能加快了药物的吸收,导致达峰时间缩短。

Objective To investigate the pharmacokinetic characteristics of amlodipine besylate among Tibetan healthy human body living in plateau.Methods A total of 8 Tibetan healthy subjects living in plateau were recruited for this study,and all subjects were given a single dose of 5 mg of amlodipine besylate orally,and venous blood samples were taken at time points of 0 h before administration and 1,2,4,8,24,48,72 h after administration.High performance liquid chromatography-mass spectrometry/mass spectrometry was used to determine amlodipine besylate concentration in plasma,and Drug And Statistics 3.0 software was used to calculate the pharmacokinetic parameters.Results The average pharmacokinetic parameters of 8 Tibetan healthy subjects who were given a single dose of 5 mg of amlodipine besylate orally were as follows,the peak time was(4.4±2.5)h,the maximum plasma drug concentration was(3.1±0.5)μg/L,the half-life period was(40±13)h,the areas under curve of the plasma drug concentration-time at 0-72 h and 0-∞h were(115±11)μg·h/L and(159±16)μg·h/L respectively.Conclusions The average peak time of amlodipine besylate in plateau areas may be related to the impact of plateau environment on the digestive system.Changes and damages to the gastrointestinal mucosal barrier caused by plateau environment may accelerate the absorption of the drug,resulting in a shorter peak time.