用气相-电子捕获法研究硝酸甘油在人体内的药代动力学及药效学

Study on Pharmacokinetics and Pharmacodynamics of Nitroglycerin in Healthy Volunteers

应用气相－电子捕获法（ＧＣＥＣＤ）对１６名健康志愿受试者（青年组８名，老年组８名）单剂量舌下含服硝酸甘油片剂０．５ｍｇ后的药代动力学及药效学进行了研究。于用药前和用药后２、４、６、７、８、１０、１５、２０ｍｉｎ取静脉血测定，以ＭＣＰＫＰ药代动力学程序拟合药－时数据。结果表明，本药的处置符合房室开放模型。青年组与老年组比较，在Ｔ１／２Ｋａ、Ｔ１／２ｋ、Ｔｍａｘ、Ｃｍａｘ方面具有显著性差异（Ｐ＜０．０５）。在药效学方面的研究表明，随着血药浓度增高，ＭＡＰ、ＴＰＲ下降，ＨＲ、ＳＶ增高，血药浓度与各药效学指标相关性依次为ＭＡＰ＞ＨＲ＞ＳＶ＞ＴＰＲ。受试者两组间药效学指标波动范围ｔ检验ＭＡＰ、ＨＲ之间无显著性差异（Ｐ＞０．０５），ＳＶ、ＴＰＲ具有显著性差异（Ｐ＜０．０５）。

Sixteen healthy volunteers (young group 8, old group 8) were given with nitroglycerin (0.5mg) sublingualy, the pharmacokinetics and pharmacodynamics were studied by gas chromatographic electron capture detector. The blood samples were determined before and after 2, 4, 6, 7, 8, 10, 15, 20minutes treatment respectively. MCPKP pharmacokinetics program was applied to imitate concentration time data. Nitroglycerin showed one compartment open model. There was significant difference in T 1/2 Ka, T 1/2 k, T max and C max between young group and old group ( P <0.05). According to pharmacodynamics, the results showed that following nitroglycerin concentration increasing, HR and SV were increased, MAP and TPR were decreased. The relationship between the blood concentration and pharmacodynamics was MAP>HR>SV>TPR. There was no significant difference in the wave range of pharmacodynamics indexes of MAP and HR, but there was significant difference of SV and TPR between two groups through t test.