The Influence of Monotherapy with Oxprenolol and Nitrendipine on Ambulatory Blood Pressure in Hypertensives

We investigated whether beta-blockers or calcium-antagonists might be preferred in baseline antihypertensive therapy. In middle-aged male patients with essential BP readings did not differ between patients on Oxpranolol or on Nitrendipine (average BP: 123 12/81 14 vs. 129 17/80 10 mmHg), when clinical casual BP was within the normotensive range. Average BP at work was lower than clinical casual BP taken at the same day (125 14/80 12 vs. 133 12/87 13 mmHg). A linear dependency between SBP at work and level of self reported physical activity (F(3,413) = 7.6; p 0.001) and arousal was found (F(3, 374) = 5.2; p 0.02). Patients on Oxprenolol consistently had lower SBP at a particular level of physical activity and at lower levels of arousal than patients on Nitrendipine. We conclude that both regimen were equally effective as baseline antihypertensive monotherapy.     

国产尼群地平和Bayer尼群地平生物利用度的比较

目的 比较中国老年收缩期高血压（ＳＹＳＴ－Ｃｈｉｎａ）和欧洲老年收缩期高血压（ＳＹＳＴ－Ｅｕｒ）两个大规模临床试验的一线药物中国资寿尼群地平和德国皋尔尼群地平在体外溶解在０．１Ｎ的盐酸溶剂中，观察其完全溶解所需时间，用高效液相半自动测定溶解的尼群地平浓度，计算并比较两种片溶解速率相似性因子ｆ２。用随机、交叉比较方法，分别给９个男性健康志愿者口服４０ｍｇ资寿尼群地平或皋尔尼群地平，采用高效液相紫外荧     

尼群地平对高血压患者左室舒张功能和细胞内钙浓度的影响

观察２３例高血压患者尼群地平治疗４周后舒张功能指标，淋巴细胞风下浓度、红细胞Ｃａ＾２＋ －ＡＴＰ酶和血浆钙调素的变化。结果显示，尼群地平可增大Ｅ／Ａ比值、快速充盈分数和１／３充盈分数，减小Ａ峰流速，房综期充盈分数和左房内径。提示尼群地平可改善左室舒张功能，尼群地平降低细胞内钙浓度，并与左房排空指数和１／３充盈分数增大呈正相关。     

尼群地平共研粉末的制备及大鼠体内药动学

目的:研究难溶性药物尼群地平共研粉末在大鼠体内的药动学。方法:采用HPLC-UV法,测定大鼠灌胃尼群地平共研粉末(T)和物理混合粉末(R)后不同时间点的血药浓度,绘制药-时曲线,计算药动学参数及相对生物利用度。结果:大鼠灌胃相当于尼群地平20mg的T和R后,血浆中尼群地平的tmax分别为(1.6±0.5)和(2.0±0.7)h;Cmax分别为(496.2±215.1)和(260.6±56.9)μg.L-1;用梯形法计算,AUC0-t分别(4 077.0±1 487.3)μg.h.L-1和(2 438.1±1 039.8)μg.h.L-1。与物理混合粉末R相比,尼群地平共研粉末T的相对生物利用度为209.27%。结论:尼群地平共研粉末与尼群地平物理混合粉末相比,在大鼠体内吸收迅速、生物利用度高。     

中国老年收缩期高血压临床试验总结报告

目的研究降压治疗能否降低老年收缩期高血压患者的脑卒中和其它心血管并发症的发生和死亡率。方法采用随机、安慰剂对照的研究方法。入选病例总数为２３９４例。１２５３例患者分入尼群地平组，尼群地平的用量为１０～４０ｍｇ／ｄ，必要时加用卡托普利１２．５～５０ｍｇ／ｄ和（或）双氢克尿噻１２．５～５０ｍｇ／ｄ。１１４１例患者分入对照组，给予相应的安慰剂治疗。结果入选时坐位血压的平均值为１７０．５／８６．０ｍｍＨｇ（１ｍｍＨｇ＝０．１３３ｋＰａ），平均年龄６６．５岁，总胆固醇５．１ｍｍｏｌ／ｌ，经过４年的随访，治疗组和对照组血压均明显下降，两组间坐位收缩压和舒张压差异分别为８．０ｍｍＨｇ和３．２ｍｍＨｇ。经过降压治疗脑卒中降低了３８％（Ｐ＝０．０１），全病因死亡率降低了３９％（Ｐ＝０．００３），心血管病死亡率降低了３９％（Ｐ＝０．０３），致死性脑卒中降低了５８％（Ｐ＝０．０２），所有的致死和非致死性心血管事件降低了３７％（Ｐ＝０．００４）。结论每治疗１０００例老年收缩期高血压患者５年可减少５５例死亡，３９例脑卒中或５９例主要的心血管事件的发生。     

Calcium-channel blockers and sodium intake: A controlled study in patients with essential hypertension

Summary Thirteen patients with mild to moderate essential hypertension and whose average supine blood pressure with no treatment was 165/104 mmHg were studied as inpatients for 3 consecutive one-week periods on different sodium intakes. On the last day of each dietary period, they received a single, 20-mg nitrendipine tablet and blood pressure was monitored every 10 minutes for 2 hours after drug administration.Nitrendipine significantly lowered blood pressure independently of the level of sodium intake, and the maximum blood-pressure lowering effect was achieved approximately 1 hour after the dose. The blood-pressure lowering effect of nitrendipine was greater on high sodium intake as compared to low sodium intake (p<0.02), and it was also greater with higher initial blood pressures. However, the sodium-related effect on blood pressure was, at least in part, independent of the pretreatment blood pressure.These results suggest that calcium antagonists, such as nitrendipine, are effective in reducing blood pressure in patients with essential hypertension and could be drugs of choice in those who are unable to restrict their salt intake.     

尼群地平在正常人血中的浓度和药效学

本文用高效液相色谱(HPLC)在5名健康受试者口服40 mg尼群地平后测定血药浓度,并同时进行药效学研究。结果表明,尼群地平的药物动力学参数分别为:T_(1/2)=5.4±3.6h;C_(max)=138.9±52ng/ml;T_(max)=2.45±1.38h;AUC_(0～16h)=724.54±365.9ng·h/ml。在药效学方面,血压和心率的变化被选作药效学指标。给药后对收缩压未见显著影响,但可引起舒张压显著的降低,并使脉压增加。如在1.5h,舒张压下降0.85 kPa(9％,P<0.01),脉压增加0.91kPa(18.1％,P<0.05)。在给药后15min到8h,心率也有显著增加,其P<0.05或0.01;在舒张压降低较甚时,心率增加尤甚。如在2h,由正常值69次/min增至86次/min(增加24.6％,P<0.01)。综观其降压作用和心率变化,是随尼群地平的血浓度变化而变化。此种作用可维持8h。     

Inter- and intra-subject variability of nitrendipine and the effects of food

Summary Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers.On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high.On a fourth occasion, the subjects took the tablet after a standard meal.The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.     

2-(3-硝基亚苄基)乙酰乙酸乙酯的合成

2- ( 3-硝基亚苄基 )乙酰乙酸乙酯 ( 1 ) [1] 是合成中轻度高血压治疗药物尼群地平 ( nitrendipine)的中间体[1] 。本文参考文献[1～ 3 ] ,以间硝基苯甲醛 ( 2 )和乙酰乙酸乙酯 ( 3)为原料 ,硫酸为催化剂合成 1 ,并对催化剂的加入顺序进行了探讨。A法 :先在 3中滴加硫酸 ,再加入 2 ,由于在 2的溶解过程中同时也将生成 1结晶 ,二者混合成为糊状物 ,导致反应不充分 ,后处理困难 ,收率低 ,产品质量差 ;B法 :先将 3与 2混合 ,再缓慢滴加硫酸 ,随着酸的加入醛很快溶解 ,接着产物结晶开始生成 ,结晶颗粒大 ,后处理容易 ,3及硫酸用量少 ,反应时间…