非洛地平片在人体内药动学与药效学的相关性研究

目的:研究非洛地平片在人体内药动学与药效学的相关性。方法:采用液-质联用法测定10名健康受试者单剂量口服非洛地平10mg后的血药浓度,并以DAS2.0药动学模块程序处理药-时数据及计算药动学参数。分别于服药前及服药后不同时间对收缩压(SBP)、舒张压(DBP)、心率(HR)、平均动脉压(MAP)进行监测。结果:平均药动学参数tmax、Cmax、AUC0～48、AUC0～∞、Ka、t1/2分别为(3.88±0.35)h、(5.94±1.45)μg·L-1、(61.73±15.54)μg·h·L-1、(67.62±16.09)μg·h·L-1、(0.73±0.33)h-1、(15.43±4.15)h,以不同时间血药浓度分别对SBP、DBP、HR和MAP进行回归分析,其相关系数分别为0.614 6、0.985 6、0.907 7和0.568 6。用药2～8 h内DBP下降明显(P<0.05或P<0.01)。结论:非洛地平血药浓度与药效相关,其有效血药浓度约为2.64～5.84μg·L-1,临床应用非洛地平应重点监测DBP、HR。

Study on the Relation of Pharmacokinetics of Felodipine with Its Pharmacodynamics in Healthy Volunteers

OBJECTIVE：To study the relationship between pharmacokinetics and pharmacodynamics of felodipine in healthy volunteers. METHODS：HPLC- MS was used to determine plasma concentration of felodipine in 10 healthy volunteers after given a single oral dose of 10 mg felodipine. DAS2.0 software was applied to calculate pharmacokinetic parameters and plasma concentra- tion- time data. Pharmacodynamic indexes such as SBP,DBP,HR and MAP were detected before and after medication. RESULTS： Mean pharmacokinetic parameters were as follows：tma（x3.88±0.35）h;Cma（x5.94±1.45）μg·L-1;AUC0～4（861.73±15.54）μg·h·L-1; AUC0～∞（67.62±16.09）μg·h·L-1;Ka（0.73±0.33）h-1;t1/（215.43±4.15）h. Regression analysis was applied to analyze the relationship of plasma concentration at different time with SBP,DBP,HR and MAP and those relative coefficients were 0.614 6,0.985 6, 0.907 7 and 0.568 6 respectively. DBP decreased remarkably within 2～8 h after medication. CONCLUSION：Plasama concentration of felodipine is correlated with its pharmacodynamics indexes. The effective plasma concentration of felodipine is within 2.64～5.84 μg·L-1. DBP and HR should be the key points of observation for its clinical use.