尼群地平在正常人及肾功能不全的高血压病人的体内消除及药效学比较

COMPARISON ON THE ELIMINATION AND PHARMACODYNAMICS OF NITRENDIPINE BETWEEN NORMAL VOLUNTEERS AND HYPERTENSIVE PATIENTS WITH IMPAIRED RENAL FUNCTION

本文以尼莫地平为内标，建立了检测血浆中尼群地平浓度的快速、灵敏的高效液相色谱方法。应用本方法进行了１６例正常人及肾功能不全的高血压患者口服尼群地平４０ｍｇ后体内消除及药效学研究。８名健康志愿者的药代动力学参数：Ｃｍａｘ６１．２１±１０．１９μｇ／ｍｌ，Ｔｍａｘ２．６５±０．４９ｈ，Ｋｅ０．１８９３±０．０７２７．Ｔ＿（１／２β）４．２３±１．８３ｈ。８名肾功能不全伴高血压的病人Ｋｅ０．１７１４±０．０１９３．Ｔ＿（１／２β）４．０９±０．５１ｈ。两组的Ｔ＿（１／２），Ｋｅ及同时间点的血药浓度在统计学上均无显著差异，提示该药在肾功能不全的病人与功能正常者消除过程一致。尼群地平在健康志愿者及高血压患者降压作用明显，血药浓度与降压作用有良好相关性，降压作用维持时间长，高血压患者尤为明显。本药具有急性排钠利尿作用，用药后血中血管紧张素Ⅱ明显升高，但肾素及醛固酮无明显变化，表明临床合并应用降压药时，以选用β受体阻滞剂或血管紧张素转换酶抑制剂为佳。

A rapid and sensitve HPLC method for the determination of nitrendipine(NTD)in human plasma was developed. Ed.Nimodipine was used as the internal standard.The pharmacokinetics and pharmacodynamics of NTD in human were studied after a single dose of 40 mg orally.The pharmacokinctic parameters in eight healthy volunteers(Group A)were Cmax 61.21±10.19 μg/l.Tmax 2.65±0.49h,Ke 0.1893±0.0193 h-1,T1/2β4.23±1.83h;but in eight patients(Group B)with impaired renal function associated with hypertensive, Ke 0.1714±0.0727 h-1,T1/2β4.09±0.51 h.No statistical difference was found in T1/2,Ke and plasma NTD concentration bewteen two groups, so the elimination of NTD in patients with impaired renal function was same as the subject with normal renal function. There was a linear relation bewteen lower blood pressure and plasma NTD concentration. NTD lowered pressure for a long time,especially in hypentensive patient. It had the effect of acute natruresis and diuresis.It increased All but did not chang PRA and ALD.We sugguest that it should useβ-blocker or angiotensin-coverting enzyme inhibitors,when it combined with other antihypertensive drug.