氨氯地平在健康人体内的药动学和药效学

Study on the pharmacokinetics and pharmacodynamics of amlodipine in healthy chinese subjects

目的:研究苯磺酸氨氯地平片在健康人体的药动学,及血药浓度与降血压效应的关系。方法:24名健康受试者单次口服10 mg苯磺酸氨氯地平片,服药后不同时间采集血样,采用LC-MS-MS法测定血浆中氨氯地平浓度,采用坐位动脉收缩压(SBP)和舒张压(DBP)的变化值为降压药效指标。结果:氨氯地平体内代谢呈二室模型,消除半衰期约36 h,表观分布容积较大,提示为全身分布,峰浓度约为(6.1±1.5)ng.mL-1。动脉收缩压和舒张压在用药后呈波动性下降,用药10 h后药效逐渐消失,可见一个药效滞后环。AUC0-120 h(ng.h.mL-1)和AUEC0-48(mmHg.h-1)分别为(237.1±77.2)和(126.1±49.8)(SBP)、(192.6±47.7)(DBP);Cmax(ng.mL-1)和Emax(mmHg)分别为(6.1±1.5)和(6.3±3.2)(SBP)、(10.1±2.9)(DBP);tmax(h)和TEmax(h)分别为(3.9±0.7)和(8.1±2.3)(SBP)、(9.2±1.2)(DBP)。结论:苯磺酸氨氯地平对动脉收缩压和舒张压均有降低作用,药效达峰时间在给药后6～10 h,均呈现较好的滞后效应。

OBJECTIVE To study the pharmacokinetics and pharmacodynamics of amlodipine in healthy subjects and explore the relationship between the blood concentration of amlodipine and the antihypertensive effect. METHODS 24 male volunteers were administered 10 mg amlodipine by single dose.The blood samples of different time points in these subjects were sampled and the drug concentrations of amlodipine were analyzed by LC-MS-MS,and the primary variables measured in this study were systolic and diastolic blood pressure（SBP and SDP） and pulse rate in a sitting position. RESULTS Amlodipine was a two-compartment model with slow elimination（t1/2,36 h） and a large apparent volume of distribution.The Cmax was（6.1±1.5）ng·mL-1.SBP and SDP were depressed after administration,and it was related to the change of drug concentration.The efficacy hysteresis rings were found from the curves of efficacy-concentration. CONCLUSION Amlodipine can depress the SBP and DBP with efficacy hysteresis.The most efficacy Emax（SBP：6.3±3.2 mmHg,DBP：10.1±2.9 mmHg） was appeared after administration 6-10 h.The efficacy hysteresis was better form on the antihypertensive effect in clinical therapy.