尼群地平治疗原发性高血压患者的药效学和药物动力学

原发性高血压14例(男11例,女3例;年龄54±s4a),首次口服尼群地平20mg2-3h后,消除T_(1/2)为3.8±1.4h,T_(max)4.4±1.5h,总外周阻力、平均动脉压分别下降40％,20％,降压作用持续12h。尼群地平10-20mg,qd或bid,口服3-4wk后,血压仍有明显下降(P<0.05),且对心率、心排血量、血糖、酯质代谢及肝、肾功能等无明显影响,适用于老年患者。     

尼群地平治疗高血压的血流动力学变化

本文报告使用国产尼群地平20mg治疗14例高血压病的急性血流动力学变化。发现它具有较强降压效应,有效率79％,血压平均下降3.4/1.9kPa(26/15mmHg)。超声心动图检查发现左心室收缩与舒张期腔径减小,射血分数和平均周径纤维缩短率增大,总周围血管阻力降低,但心率、心搏量与心输出量无变化。提示尼群地平在体内同时具有动、静脉扩张作用。     

尼群地平对高血压患者静息和运动时血压和心率的影响

尼群地平对高血压患者静息和运动时血压和心率的影响刘健，李佐才，王明英用症状限制性极量运动试验评价高血压患者一次口服尼群地平（ＮＴ）２０ｍｇ对静息和运动的血压、心率、血压心率双乘积和运动耐量的影响。资料与方法按ＷＨＯ高血压诊断标准确诊的高血压患者３０例...     

尼群地平治疗老年收缩期高血压的疗效观察

观察尼群地平对老年收缩期高血压疗效，结果４６例中１ｍｏ内总有效率８２．６％，１ａ后９３．４８％，２ａ后９７．８３％，与治疗前比较Ｐ〈０．０１。     

尼群地平在高血压病中的临床应用

尼群地平是目前正在临床试用的新钙离子拮抗剂。本文介绍它的血流动力学效应、对高血压病的治疗作用及其药代动力学;并指出它是一个十分有前途的降压药物,作用时间长而不良反应较小。     

尼群地平可生物降解微球和原位凝胶的药物动力学

目的研究尼群地平可生物降解微球和原位凝胶在家兔体内的药物动力学特征。方法采用HPLC法,测定3只健康家兔肌注尼群地平微球及原位凝胶(分别为受试制剂A、B)和尼群地平溶液(参比制剂C)后不同时间点的血药浓度,绘制药时曲线,计算药物动力学参数及相对生物利用度。结果家兔肌注相当于尼群地平30 mg的制剂A、B和C后,血浆中尼群地平的tmax分别为3、1和1 h;cmax分别为(468±30)、(2259±272)和(2777±445)nmol.L-1;用梯形法计算,AUC0~t分别为(1193±249)、(1716±268)和(2257±199)nmol.d.L-1。与参比制剂C相比,受试制剂A、B的相对生物利用度分别为(52.15±11.54)%和(76.37±14.00)%。lnAUC0~t在制剂A和C间有显著性差异,在B和C、A和B之间无显著性差异,在个体间均无显著性差异(P>0.05),受试制剂A和B的AUC0~t90%置信区间分别为参比制剂的23.85%~110.57%和39.15%~145.75%。结论尼群地平可生物降解微球和原位凝胶与尼群地平溶液相比,在家兔体内具有更长的作用时间,但相对生物利用度较低。     

尼群地平治疗高血压45例临床分析

尼群地平(Nitrendipine)是一种抗高血压新型药物,属二氢毗啶类钙离子拮抗剂,有明显血管扩张作用,降压作用缓和而持久,本文就尼群地平治疗45例高血压的疗效观察报告如下。临床资料病例选择选择原发性高血压能密切配合治疗者45例。男25例,女20例;年龄32—78岁(平均52岁);病程3—25年(平均8年)。按世界卫生组织诊断标准临界性高     

氨氯地平与尼群地平治疗老年高血压病的比较

目的：比较氨氯地平与尼群地平治疗老年高血压病的疗效。方法：采用随机单盲平行对照法，氨氯地平组４１例（男性２９例，女性１２柳；年龄６２．７±ｓ１．０ａ），用氨氯地平５－１０ｍｇ，ｐｏ，ｑｍ×４ｗｋ治疗。尼群地平组２１例（男性１４例，女性７例；年龄６２．２±１．３ａ）用尼群地平１０－２０ｍｇ，ｐｏ，ｑ１２ｈ×４Ｗｋ治疗。结果：氨氯地平组降压总有效率９３％，与尼群地平组的８６％相似（Ｐ＞０．０５）；氨氯地平组尚有显著降低三酰甘油及血糖的作用；不良反应发生率氨氯地平组１５％显著低于尼群地平组的２１％（Ｐ＜０．０１），且反应轻微，无１例终止治疗。结论：氨氯地平降压疗效好，且优于尼群地平。     

Pharmacokinetics of bendroflumethiazide in hypertensive patients

Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml^–1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg^–1. Non-renal clearance averaged 200 ml · min^–1. The renal clearance of bft was significantly lower (p<0.05) after 5 mg (48 ml · min^–1) than after 2.5 mg bft (93 ml · min^–1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.Supported by the Swedish Medical Research Council (Grant No. B77-19X-00227-13) and Ferrosan AB, Malmö, Sweden.     

氨氯地平与尼群地平治疗高血压病的比较

目的：比较氨氯地平与尼群地平治疗高血压病的疗效。方法：高血压病Ⅰ期和Ⅱ期病人４６例（男性３４例、女性１２例；年龄５０±ｓ８ａ），用氨氯地平５ｍｇ，ｑｄ，ｐｏ×１ｗｋ，ｗｋ２每日增加１次剂量，最大剂量１０ｍｇ，ｑｄ；尼群地平治疗相同病人作对照，剂量为２０ｍｇ，ｂｉｄ，ｐｏ×１ｗｋ，ｗｋ２每日增加１次剂量，最大剂量２０ｍｇ，ｔｉｄ。２组均４ｗｋ为一个疗程。结果：氨氯地平组和尼群地平组显效率各为６７％和５３％，总有效率各为９１％和７９％，２组疗效无显著性差异（Ｐ＞０．０５）。短期治疗中２组皆无严重不良反应。结论：氨氯地平与尼群地平一样对高血压病的疗效显著而又安全。     

氨氯地平152例与尼群地平61例治疗高血压病的比较

氨氯地平治疗１５２例（男性９８例，女性５４例）高血压病病人，每日早餐后５－１０ｍｇ，ｐｏ，疗程４ｗｋ。并与尼群地平１０ｍｇ，ｐｏ，ｂｉｄ或ｔｉｄ，４ｗｋ治疗高血压病病人６１例（男性３５例，女性２６例）作比较。结果氨氯地平组降压显效率７０．４％，有效率１６．４％，显著高于尼群地平组（显效率５３％，有效率３２％），Ｐ＜０．０５。不良反应２组类似，主要有潮红、心悸、头晕及踝肿，总发生率以氨氯地平组为少。     

Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function

Summary The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml·min^–1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay.In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, C_max), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68).The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in C_max did not reach significance because of the large variability in each group.Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.     

The pharmacodynamics and pharmacokinetics of a new calcium antagonist nisoldipine in normotensive and hypertensive subjects

Summary The pharmacodynamic and pharmacokinetic profiles of nifedipine and nisoldipine were compared in a double blind, placebo-controlled study. Nisoldipine, 10 mg significantly reduced systolic blood pressure but nifedipine 20 mg retard did not, although both drugs had significant pharmacodynamic effects as evidenced by increased heart rates. The terminal elimination half-life in plasma was similar for both drugs with a mean of 2 h. The pharmacodynamics of nisoldipine were studied in 8 hypertensives following both acute and chronic administration. Antihypertensive efficacy was demonstrated after acute dosing and was maintained over 4 weeks of twice daily treatment as monotherapy.     

Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE-inhibitor imidapril in hypertensive patients

Aims To investigate the pharmacokinetic profile of the ACE-inhibitor imidapril in 10 hypertensive patients after a first single dose (10  mg) and after 28 days therapy with imidapril 10  mg once daily.
Methods C _max, t _max, t _1/2 and AUC of imidapril and imidaprilat were obtained. ACE-activity and arterial blood pressure during imidapril were corrected by a preceding placebo-investigation.
Results The AUC of imidapril was 140 (43  s.d.)  ng  ml⁻¹ h after the first dose and 123 (34  s.d.)  ng  ml⁻¹ h at steady state. AUC of the active moiety imidaprilat averaged 211 (101  s.d.)  ng  ml⁻¹ h after the first dose and 240 (55  s.d.)  ng  ml⁻¹ h at the steady state investigation. Maximal ACE-inhibition was 75% after the single dose as well as at steady state. ACE inhibition before drug intake at day 28 (i.e. trough) was 50%. The (placebo-corrected) maximal drop in diastolic blood pressure after imidapril was 22  mmHg after the first dose and 25  mmHg at steady state. Exploratory analysis of imidaprilat plasma concentration vs effect profiles suggests a hyperbolic concentration effect relationship where data of the single dose contribute to the ascending part of an E_max-curve, whereas the plateau around E_max is maintained at steady state.
Conclusions In this group of hypertensive patients, the pharmacokinetic profile and the drop in ACE-activity as well as in blood pressure seen after a single dose of imidapril and at steady state were similar. The initial response to a test dose might therefore predict the response during chronic dosing.     

Pharmacodynamics and pharmacokinetics of three different doses of urapidil infused in hypertensive patients

Summary The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33±8 mmHg, the 65 mg dose a maximum decrease of 39±12 mmHg and the 130 mg dose a maximum decrease of 50±12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses. In severe hypertension, the 130 mg dose can be employed, since it does result in a further, significantly larger decrease in blood pressure.     

Pharmacodynamics and pharmacokinetics of oral nitrendipine solution in hypertensive patients with advanced renal failure

Summary Nitrendipine solution 5 mg·ml^–1 in the dose of 5 mg was given orally to 20 patients with chronic renal failure and elevated diastolic blood pressure (110 mmHg), of whom 10 were on maintenance haemodialysis (endogenous creatinine clearance <5 ml·min^–1) and 10 were at the predialysis stage (endogenous creatinine clearance 5–20 ml·min^–1).The aim of the study was to investigate the influence of kidney function and/or dialysis treatment on the pharmacokinetic and pharmacodynamic profile of a solution of nitrendipine and to assess its antihypertensive efficacy.After 10 min there was a significant reduction in blood pressure from 188/113 to 173/100 (patients not dependent on dialysis) and from 197/112 to 161/94 mmHg (patients dependent on dialysis). The maximum fall in blood pressure (approximately 30%) was attained after 90 min in the dialysis patients and after 120 min in the non-dialysis group. Blood pressure increased again about 3 h after the administration of nitrendipine but it was still below baseline after 12 h. The terminal elimination half-life (4.1 h in the dialysis patients and 3.6 h in non-dialysis patients) was similar to that observed in patients with normal renal function. The pharmacokinetics of nitrendipine did not differ between the dialysis and non-dialysis groups. There was a correlation between plasma concentration and the blood pressure reduction. The maximum plasma concentration of nitrendipine was reached after 0.5 h (median) and did not differ between the two groups. The mean maximum plasma concentration was 14.8 g·1^–1 in the study population as a whole, with comparable means in the dialysis (17.3 g·1^–1) and non-dialysis (12.4 g·1^–1) groups.The nitrendipine solution proved to be effective in lowering acutely elevated blood pressure in patients with advanced renal failure and renal hypertension, and was well tolerated. The pharmacokinetics was not affected by renal impairment or by dialysis.     

The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives

Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined -blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.