尼莫地平在老年人体内药动学与药效学相关性研究

A STUDY ON THE RELATION OF PHARMACOKINETICS AND PHARMACODYNAMICS OF NIMODIPINE IN THE ELDERLY

①目的 研究尼莫地平在老年人体内药动学与药效学的相关性。②方法 采用高效液相色谱法测定 10名健康老年志愿受试者单剂量口服 6 0mg尼莫地平后的血浆药物浓度 ,并用GP 30 3血流动力学测定仪测量平均动脉压 (MAP)、心率 (HR)、每搏量 (SV)、体循环阻力 (TPR)。③结果 服药后 5 1.36min血药浓度达到高峰 ,6 0 .0 0min药效达到高峰。平均药动学参数Ka、K、T1/ 2K、Tmax、Cmax、AUC分别为 (0 .0 4 6± 0 .0 19)min-1、(0 .0 10±0 .0 0 4 )min-1、(80 .88± 4 4 .75 )min、(5 1.36± 16 .4 7)min、(2 9.0 5± 2 0 .6 2 ) μg·L-1、(42 91.36± 2 377.18) μg·min·L-1,以不同时间血药浓度分别对MAP、HR、SV、TPR进行回归分析 ,其相关系数分别为 0 .971、0 .74 6、0 .6 35、0 .4 6 5。④结论 尼莫地平血药浓度与药效相关 ,临床应用尼莫地平应重点观察MAP。

Objective To study pharmacokinetics and pharmacodynamics of Nimodipine in the aged. Methods HPLC was used to detect blood concentration of Nimodipine and GP-303 instrument for pharmacodynamic indexes such as MAP, HR, SV and TPR in 10 senior healthy volunteers after they were given 60 mg of single-dose Nimodipine, orally. Results Nimodipine reached its peak blood concentration in 51.36 min and showed its best function in 60.00 min. The mean pharmacokinetics parameters such as Ka,K,T 1/2K,T max,C max,AUC were (0.046±0.019)min -1,(0.010±0.004)min -1,(80.88±44.75)min,(51.36± 16.47)min,(29.05±20.62)μg·L -1 and (4 291.36±2 377.18)μg·min·L -1, respectively. The regression of blood concentration in different time was made and the relative coefficients of MAP,HR,SV and TPR were 0.971, 0.746, 0.635 and 0.465, respectively. Conclusion The blood concentration of Nimodipine is correlated with its pharmacodynamics. The MAP and HR should be the key points of observation for its clinical use.