BACKGROUND & AIMS: OBJECTIVES:Lipoprotein oxidation, dyslipidemia, and hypertension are important underlying causes of accelerated atherosclerosis in patients with diabetes mellitus. The potential of antihypertensive medications to reduce lipid oxidation is, therefore, an important determinant in the choice of agents for patients with diabetes mellitus. The aim of this study was to compare the lowering effect of a new dihydropyridine calcium antagonist, lercanidipine, with that of the first angiotensin-receptor blocker, losartan, on low-density lipoprotein (LDL) oxidation. METHODS:Forty patients in metabolically stable condition who had type 2 diabetes mellitus with hypertension were studied in this single-blind, randomized, prospective crossover study, comprising 2 treatment periods of 16 weeks each, separated by a 4-week washout period. LDL oxidation was evaluated by dialdehyde analysis by means of the thiobarbituric acid-reactive substances assay with and without cupric sulfate, as well as determination of conjugated dienes in the LDL lipid extract. RESULTS:Lercanidipine and losartan both significantly reduced the propensity of the serum to oxidize LDL (P =.001). With one method of estimation (conjugated dienes), the effect of lercanidipine was superior to that of losartan (P =.04). Losartan lowered urinary albumin excretion but lercanidipine did not. CONCLUSIONS:Both lercanidipine and losartan attenuate LDL oxidation in patients with type 2 diabetes mellitus and hypertension. This observation may offer insight into the mechanisms of the therapeutic effects of these agents in patients with diabetes mellitus.

背景与目标： 目的：脂蛋白氧化，血脂异常和高血压是糖尿病患者加速动脉粥样硬化的重要根本原因。因此，降压药减少脂质氧化的潜力是选择糖尿病患者用药的重要决定因素。这项研究的目的是比较一种新型的二氢吡啶类钙拮抗剂lercanidipine和第一种血管紧张素受体阻滞剂losartan对低密度脂蛋白（LDL）氧化的降低作用。
方法：在这项单盲，随机，前瞻性交叉研究中，对40名代谢稳定状态的2型糖尿病合并高血压患者进行了研究，该研究包括2个治疗期，每个治疗期16周，相隔4周的清除期。 LDL的氧化通过二醛分析来评估，方法是在有或没有硫酸铜的情况下，通过硫代巴比妥酸反应性物质测定，以及测定LDL脂质提取物中的共轭二烯。
结果：乐卡地平和氯沙坦均显着降低了血清氧化低密度脂蛋白的倾向（P = .001）。用一种估计方法（共轭二烯），乐卡地平的作用优于氯沙坦（P = .04）。氯沙坦可降低尿白蛋白排泄量，而乐卡地平则不能。
结论：lercanidipine和losartan均可减轻2型糖尿病和高血压患者的LDL氧化。该观察结果可以提供对这些药物对糖尿病患者的治疗作用机理的见解。

BACKGROUND & AIMS: :The aim of this study was to evaluate the macrocirculatory and microcirculatory effects of treatment with lercanidipine, a new antihypertensive agent acting both on blood pressure and microcirculation in patients with moderate essential hypertension and without vascular disease and in patient with hypertension and vascular disease. In hypertensive subjects target-organ damage associated with high blood pressure may now be objectively documented by noninvasive tests. These alterations constitute a model to evaluate not only the pressure effects of antihypertensive treatment but also the normalization of the peripheral microcirculatory network. With color duplex scanning, flow velocity in the central retinal artery and retinal flow velocity can be measured and with use of laser-Doppler-flowmetry, it is also possible to evaluate microcirculation alterations in hypertensive subjects. These evaluation methods are completely noninvasive and may be used to assess the microcirculatory effects of antihypertensive drugs.

背景与目标： ：本研究的目的是评估在患有中度原发性高血压和无血管疾病的患者以及患有高血压和血管疾病的患者中，使用新的降压药lercanidipine治疗大环和微循环的作用。在高血压受试者中，与高血压相关的靶器官损害现在可以通过非侵入性测试客观记录。这些改变构成了一个模型，不仅可以评估降压治疗的压力效果，还可以评估周围微循环网络的正常化。通过彩色双工扫描，可以测量视网膜中央动脉的流速和视网膜流速，并且通过使用激光多普勒血流仪，还可以评估高血压患者的微循环改变。这些评估方法完全是非侵入性的，可用于评估降压药的微循环作用。

BACKGROUND & AIMS: BACKGROUND:Combination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension. METHODS:One hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥ 90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks. RESULTS:The baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P < 0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P < 0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P > 0.05), 67.1% vs. 44.7% (P < 0.05), and 71.8% vs. 45.9% (P < 0.05). There was no significant difference of side effects between the two groups. CONCLUSION:The benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.

背景与目标： 背景：联合治疗是降低高血压患者血压的有效方法。本研究旨在评估贝那普利/雷卡地平与轻度至中度高血压患者相比单独使用贝那普利的疗效和安全性。
方法：118例轻度至中度原发性高血压患者被纳入这项随机，单盲，平行组研究，并随机分为A组（苯那普利10 mg / lercanidipine 10 mg）和B组（苯那普利10毫克）持续8周。如果舒张压（DBP）保持≥90 mmHg，则在4周时将贝那普利的剂量最高滴定至20 mg。在第1、4和8周结束时评估血压控制和副作用。
结果：两组的基线特征相似。两组的血压均较基线下降（P <0.05）。在第4和第8周结束时，贝那普利/来那地平产生的BP降低量大于单独的贝那普利（P <0.05）。在第1、4和8周结束时，贝那普利/雷卡地平和贝那普利组的BP控制率比较分别为41.2％vs. 37.6％（P> 0.05），67.1％vs. 44.7％（P <0.05 ），分别为71.8％和45.9％（P <0.05）。两组之间的副作用没有显着差异。
结论：贝那普利/雷卡地平联合用药比单独使用贝那普利更能有效降低血压，但不会增加副作用的发生率。

BACKGROUND & AIMS: BACKGROUND:Irrespective of their clinical relevance, side effects cannot be considered a negligible problem in antihypertensive therapy. The aim of this trial was to evaluate the tolerability profile of lercanidipine with that of two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensives. METHODS:In a multicenter, double-blind, parallel study 828 elderly (aged > or =60 years) hypertensives were randomized to lercanidipine 10 mg/day (n = 420), amlodipine 5 mg/day (n = 200), or lacidipine 2 mg/day (n = 208) (ratio 2:1:1). If blood pressure (BP) control was unsatisfactory (systolic BP/diastolic BP > or =140/90 mm Hg), the dose of the double-blind medication was doubled and, as a further step, enalapril or atenolol (plus diuretic, if needed) was added. Patients were treated for an average of 12 months. RESULTS:Amlodipine patients had significantly (P <.001) higher rates of edema (19%) and of early study discontinuations due to edema (8.5%) compared with lercanidipine (9% and 2.1%) and lacidipine patients (4% and 1.4%). Similarly, edema-related symptoms (lower limb swelling and heaviness) occurred significantly (P <.01) more often with amlodipine (50% and 45%, respectively) than with lercanidipine (35% and 33%) and lacidipine (34% and 31%). Most edema cases occurred in the first 6 months, a between-treatment difference being evident since beginning of treatment. Other drug-related adverse events did not differ between treatments. Blood pressure was equally and effectively reduced in the three groups. CONCLUSIONS:The two lipophilic dihydropyridine calcium antagonists, lercanidipine and lacidipine, have an antihypertensive effect comparable to that of amlodipine, but a better tolerability profile.

背景与目标： 背景：无论其临床意义如何，在高血压治疗中副作用都不能被认为是可以忽略不计的问题。该试验的目的是评估乐卡地平与其他两种钙拮抗剂（氨氯地平和拉西地平）在老年高血压患者中的耐受性。
方法：在一项多中心，双盲，平行研究中，将828名老年（年龄≥60岁）高血压患者随机分为乐卡地平10 mg /天（n = 420），氨氯地平5 mg /天（n = 200）或拉西地平2毫克/天（n = 208）（比例2：1：1）。如果血压（BP）的控制效果不理想（收缩压/舒张压BP>或= 140/90 mm Hg），则双盲药物的剂量应加倍，作为进一步措施，使用依那普利或阿替洛尔（如果需要则加利尿剂）需要）添加。患者平均接受治疗12个月。
结果：与乐卡地平（9％和2.1％）和拉西地平患者（4％和1.4）相比，氨氯地平患者的水肿发生率（19％）和因水肿而导致的早期研究中断（8.5％）显着（P <.001） ％）。同样，氨氯地平（分别为50％和45％）比乐卡地平（35％和33％）和拉西地平（34％和40％ 31％）。大多数水肿病例发生在头6个月，自治疗开始以来，治疗之间存在明显差异。其他药物相关的不良事件在治疗之间没有差异。在三组中，血压均被有效地降低。
结论：两种亲脂性二氢吡啶类钙拮抗剂乐卡地平和拉西地平具有与氨氯地平相当的降压作用，但耐受性较好。

BACKGROUND & AIMS: :The influence of treatment with the dihydropyridine-type Ca2+ antagonist lercanidipine on heart and coronary microanatomic changes was investigated in spontaneously hypertensive rats, Cohen-diabetic rats, and Cohen-Rosenthal diabetic hypertensive rats. At 12 weeks of age, animals were left untreated (control groups) or were treated for 8 weeks with an oral dose of 3 mg/kg per day of lercanidipine. Wistar-Kyoto rats were used as a normotensive reference group. In spontaneously hypertensive rats and diabetic hypertensive rats, systolic blood pressure was higher in comparison with Wistar-Kyoto rats. Augmented pressure values were decreased by lercanidipine treatment. Systolic blood pressure was slightly higher in Cohen-diabetic rats than in Wistar-Kyoto rats, and this increase was countered by treatment with lercanidipine. In spontaneously hypertensive rats, diabetic rats, and diabetic hypertensive rats, the thickness of left ventricle and cardiocyte area were increased. Focal connective tissue areas and diffuse accumulation of connective tissue were observed in the left ventricle of spontaneously hypertensive and Cohen-diabetic rats, respectively. Pharmacological treatment countered left ventricle thickening and restored cardiocyte area values in subendocardium. An increased thickness of tunica media accompanied by luminal narrowing was found in coronary artery branches of control spontaneously hypertensive and diabetic hypertensive rats. Treatment with lercanidipine countered vascular changes primarily in small-sized coronary arteries. These results indicate that hypertensive, diabetic, and diabetic hypertensive rats undergo cardiac hypertrophy and vascular changes affecting small-sized coronary arteries. Treatment with lercanidipine countered hypertension-related cardiac and coronary changes, suggesting that this dihydropyridine-type Ca2+ antagonist may improve heart and coronary structure in diabetes associated with hypertension.

背景与目标： ：在自发性高血压大鼠，Cohen-糖尿病大鼠和Cohen-Rosenthal糖尿病高血压大鼠中，研究了用二氢吡啶类Ca2拮抗剂乐卡地平治疗对心脏和冠状动脉微解剖学变化的影响。在12周大时，动物不予治疗（对照组）或以每天3 mg / kg的lercanidipine口服剂量治疗8周。 Wistar-Kyoto大鼠用作血压正常对照组。与Wistar-Kyoto大鼠相比，自发性高血压大鼠和糖尿病性高血压大鼠的收缩压更高。乐卡地平治疗可增加压力值。 Cohen-糖尿病大鼠的收缩压略高于Wistar-Kyoto大鼠，而这种增加可以通过用lercanidipine治疗来抵消。在自发性高血压大鼠，糖尿病大鼠和糖尿病性高血压大鼠中，左心室厚度和心肌细胞面积增加。自发性高血压和科恩-糖尿病大鼠的左心室分别观察到局灶性结缔组织区域和结缔组织的弥漫性积聚。药物治疗可抵抗心内膜下左心室增厚和恢复心肌细胞面积值。在自发性高血压和糖尿病性高血压大鼠的冠状动脉分支中发现中膜厚度增加并伴有腔狭窄。乐卡地平的治疗主要在小型冠状动脉中抵抗血管变化。这些结果表明，高血压，糖尿病和糖尿病高血压大鼠经历心脏肥大和血管变化，影响了小冠状动脉。乐卡地平的治疗可对抗高血压相关的心脏和冠状动脉变化，提示这种二氢吡啶类Ca2拮抗剂可改善与高血压相关的糖尿病患者的心脏和冠状动脉结构。

BACKGROUND & AIMS: OBJECTIVE:The RED LEVEL study (REnal Disease: LErcanidipine Valuable Effect on urine protein Losses) directly compares, in an explorative fashion, the effects of lercanidipine + enalapril and amlodipine + enalapril combinations on renal parameters in hypertensive subjects. RESEARCH DESIGN AND METHODS:This was a 1 year, prospective, multi-center, randomized, open-label, blinded-endpoint (PROBE) study in hypertensive patients with albuminuria. MAIN OUTCOME MEASURES:Renal function (albuminuria, serum creatinine, creatinine clearance, estimated glomerular filtration rate and proteinuria); blood pressure. RESULTS:Albuminuria was significantly reduced, compared with baseline values, with the lercanidipine + enalapril combination over the entire study period; at month 3, month 6 and month 12, changes from baseline were: -162.5 (p-value = 0.0439), -425.8 (p-value = 0.0010), -329.0 (p-value = 0.0011) mg/24 h), respectively. On the other hand, this improvement was not observed with enalapril + amlodipine. Other parameters of renal function such as serum creatinine, creatinine clearance, estimated glomerular filtration rate and proteinuria did not change over the study. Both lercanidipine + enalapril and amlodipine + enalapril significantly reduced systolic and diastolic blood pressure values from baseline all over the study period with no significant differences between groups. Safety outcomes were comparable between the two groups. CONCLUSIONS:Overall, the results of this explorative study lend support to the anti-albuminuric effect of the lercanidipine + enalapril combination and to the long term renal-protective effects of this combination in patients with hypertension.

背景与目标： 目的：RED LEVEL研究（肾病：乐卡地平对尿蛋白损失的重要作用）以探索性方式直接比较了乐卡地平那拉普利和氨氯地平那拉普利组合对高血压受试者肾脏参数的影响。
研究设计与方法：这是一项针对高血压蛋白尿患者的为期1年的前瞻性，多中心，随机，开放标签，盲点（PROBE）研究。
主要观察指标：肾功能（白蛋白尿，血清肌酐，肌酐清除率，估计的肾小球滤过率和蛋白尿）；血压。
结果：在整个研究期间，使用lercanidipine®enalapril联合用药，与基线值相比，白蛋白尿明显减少；在第3个月，第6个月和第12个月时，与基线相比的变化为：-162.5（p值== 0.0439），-425.8（p值= 0.0010），-329.0（p值= 0.0011）mg / 24 h，分别。另一方面，依那普利氨氯地平未观察到这种改善。在本研究中，其他肾功能参数，例如血清肌酐，肌酐清除率，估计的肾小球滤过率和蛋白尿均未改变。在整个研究期间，lercanidipine enalapril和amlodipine enalapril均较基线显着降低了收缩压和舒张压值，各组之间无显着差异。两组的安全性结果可比。
结论：总的来说，这项探索性研究的结果为乐卡地平那那普利组合的抗白蛋白尿作用以及该组合对高血压患者的长期肾脏保护作用提供了支持。

BACKGROUND & AIMS: :This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.

背景与目标： ：这项随机，双盲，双虚拟，平行组，多中心研究比较了乐卡地平和拉西地平的疗效和耐受性。入选了患有单纯收缩期高血压（仰卧血压> / = 160 / <95 mmHg）的老年患者，并进行了14-27天的安慰剂磨合期，然后每天随机分配一次10 mg lercanidipine片（n = 111）或拉西平片2 mg每天一次（n = 111），用于评估期（112-160天）。如果需要，允许在8周后滴定至每天20 mg乐卡地平（两次10 mg片剂）或lacidipine 4 mg每天滴定（两次2 mg片剂）滴定。在磨合期结束和评估期结束之间，两种治疗均降低了仰卧位和站立时的收缩压和舒张压（P <0.0001）。在评估期结束时，仰卧收缩压的估计平均治疗差异（95％置信区间）为-0.81（-4.45，2.84）mmHg。这些置信区间在等效的指定限制内​​，即（-5，5）mmHg。动态血压监测表明，这两种药物的降压作用持续了整个24小时的服药期间，并遵循了昼夜节律模式。两种疗法均具有良好的耐受性，药物不良反应发生率低，停药率低。乐卡地平退出治疗的患者明显减少（P = 0.015）。两种疗法均未对脉搏率或心脏传导产生任何临床显着影响。总之，两种治疗方法在控制单纯收缩期高血压患者的仰卧收缩压方面均有效。

BACKGROUND & AIMS: INTRODUCTION:Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities. METHODS:This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated. RESULTS:27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval [CI] 16.5-24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2-12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study. CONCLUSION:Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers.

背景与目标： 简介：钙通道阻滞剂是公认的治疗高血压的方法。然而，尽管有许多有效的药物可供使用，高血压控制仍然很差。原因之一是不良事件导致的耐受性差。种族差异也存在。第三代钙通道阻滞剂乐卡地平具有更好的耐受性。但是，尚未在亚洲人口中进行研究。这项研究检查了其在不同种族的亚洲受试者中的疗效和耐受性。
方法：这是一项为期八周的开放标签研究，研究对象为轻度至中度高血压的成年人。在基线时进行了血压（BP），脉搏率，自我管理的症状检查和实验室评估。为患者开具10 mg lercanidipine的处方药，如果在第4周未控制血压，则滴定至20 mg，在第8周重复进行基线评估。还列举了不良事件。
结果：27名患者（平均年龄53.4 /-12.1岁）完成了研究。基线收缩压（SBP），舒张压（DBP）和心率分别为159 /-12.2、96.6 /-7.7 mmHg和71 /-13 / min。代表了三个种族群体。治疗四个星期后，SBP和DBP显着下降。在第8周发现进一步降低到139 /-14.3和88 /-9.8（p值小于0.0001）。SBP和DBP的绝对降低为20.5 mmHg（95％的置信区间[CI] 16.5-24.5，p -值小于0.0001）和9.3 mmHg（95％CI 6.2-12.5，p值小于0.0001）。在研究结束时，除心以外的所有不良症状均得到减轻。
结论：乐卡地平在不同种族的亚洲人中有效且耐受性良好。在亚洲人中，其降低血压的作用和耐受性似乎与其他有关高加索人和其他钙通道阻滞剂的研究相似。

BACKGROUND & AIMS: :A simple and sensitive spectrophotometric method has been developed for the assay of lercanidipine hydrochloride (LER) in bulk and in formulations. The method is based on the formation of coloured species between the drug and 1,2-naphthaquinone-4-sulphonic acid sodium salt (NQS) by means of nucleophilic substitution reaction. Absorbance was measured at λ(max) = 460 nm. The method was analyzed statistically. The system obeyed the Beer's law in the range 20-100 μg mL⁻¹. Molar absorptivity value was found to be 4.79 × 10³ L mol⁻¹ cm⁻¹. Limits of detection and quantification were found to be as low as 0.04 and 0.13 μg mL⁻¹. Precision (RSD, 0.4%) and accuracy (recovery 99.2 ± 0.6 to 101.1 ± 0.8%) of the developed method were evaluated.

背景与目标： ：已经开发了一种简单而灵敏的分光光度法，用于测定大批量和制剂中的盐酸乐卡地平（LER）。该方法基于通过亲核取代反应在药物和1,2-萘醌-4-磺酸钠盐（NQS）之间形成有色物质。在λ（max）= 460 nm处测量吸光度。对该方法进行了统计分析。该系统遵从比尔定律，范围为20-100μgmL -1。发现摩尔吸收率值为4.79×10 3 L mol -1 cm -1。发现检测和定量限低至0.04和0.13μg/ mL。评价了所开发方法的精密度（RSD，0.4％）和准确度（回收率99.2±0.6至101.1±0.8％）。

BACKGROUND & AIMS: OBJECTIVE:The objective of this study was to compare the effectiveness of lercanidipine with felodipine in patients with mild-to-moderate hypertension on day-to-day home blood pressure variability. METHODS:This is a sub-study of a multicenter, randomized, open-label, parallel group and active controlled clinical trial. Hypertensive patients aged 18-75 (i.e. diastolic blood pressure ≥90 mmHg and <110 mmHg; systolic blood pressure ≥140 mmHg and <180 mmHg) and 24 h mean BP >130/80 mmHg) were eligible for this study. During the study, blood pressure (BP) and heart rate (HR) were recorded. The day-to-day BP variability (BPV) and HR variability (HRV) were obtained by the standard deviation (SD) of daily BP/HR average (of six readings) in 7 days. RESULTS:There were 186 patients (89 and 97 patients in the lercanidipine and felodipine groups, respectively) included in this study. Lercanidipine hydrochloride 10 mg/d and felodipine sustained-release tablets 5 mg/d were given to their respective groups. After 6 weeks of treatment, SD of home BP significantly reduced compared with baseline in both groups (P < .05) while SD of home HR also changed significantly after treatment (P < .05). There was no significant difference in SD of home BPV between the lercanidipine and felodipine groups after treatment. CONCLUSION:Treatment with lercanidipine and felodipine both resulted in reduction of BPV and HRV. There was no significant inter-group difference in reduction of BPV between the groups. Lercanidipine is an effective antihypertensive drug in improving BPV. National clinical trial: NCT01520285.

背景与目标： 目的：本研究的目的是比较乐卡地平和非洛地平在轻度至中度高血压患者日常家庭血压变异性方面的有效性。
方法：这是一个多中心，随机，开放标签，平行组和主动对照临床试验的子研究。年龄在18-75岁的高血压患者（即舒张压≥90 mmHg和<110 mmHg;收缩压≥140mmHg和<180 mmHg）和24 h平均BP> 130/80 mmHg）符合本研究的条件。在研究过程中，记录了血压（BP）和心率（HR）。每天的BP变异性（BPV）和HR变异性（HRV）是通过在7天内每日BP / HR平均值（六个读数）的标准偏差（SD）获得的。
结果：本研究共纳入186例患者（乐卡地平组和非洛地平组分别为89例和97例）。分别给予盐酸乐卡地平10μmg/ d和非洛地平缓释片5μmg/ d。在治疗6周后，两组的家庭BP的SD与基线相比均显着降低（P while <.05），而治疗后家庭HR的SD也有显着变化（P <.05）。治疗后，乐卡地平组和非洛地平组的家庭BPV SD没有显着差异。
结论：乐卡地平和非洛地平治疗均可降低BPV和HRV。两组之间的BPV降低之间没有显着的组间差异。乐卡地平是改善BPV的有效降压药。国家临床试验：NCT01520285。

BACKGROUND & AIMS: :Achieving optimal blood pressure (BP) control is the most important single issue in the management of hypertension, and in most patients, it is difficult or impossible to achieve target levels with one drug. Blocking two or more regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed-dose combination therapy is an efficacious, relatively safe and cost-effective treatment option in most patients with essential hypertension. Of note, the once-daily administration of a fixed-dose enalapril/lercanidipine, by bringing together two distinct and complementary mechanisms of action, reduces BP effectively and has the potential for improved target organ protection relative to either class agent alone.

背景与目标： ：实现最佳血压（BP）控制是高血压管理中最重要的单个问题，在大多数患者中，用一种药物很难或不可能达到目标水平。阻断两个或两个以上的调节系统可以更有效，更生理地降低BP，目前的指南建议将联合治疗作为一线治疗或在高血压治疗的早期使用。在大多数原发性高血压患者中，固定剂量联合治疗是一种有效，相对安全且具有成本效益的治疗选择。值得注意的是，每天固定剂量的依那普利/拉卡地平的每日给药，通过将两种不同且互补的作用机制结合在一起，可有效降低血压，并且相对于单独使用任一类药物而言，都有改善靶器官保护的潜力。

BACKGROUND & AIMS: OBJECTIVES:Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure. DESIGN AND METHODS:In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations. RESULTS:For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p < 0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals. CONCLUSIONS:These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon.

背景与目标： 目的：血管重塑和肥大是降压治疗的早期治疗目标。本研究旨在评估高度血管选择性钙通道阻滞剂lercanidipine（10 mg /天）或利尿剂氢氯噻嗪（25 mg /天）的1年给药对高血压相关血管改变的影响。该研究还旨在评估是否以及在何种程度上：（i）血管肥大的药理学退化仅与血压（BP）降低“本身”有关，或与给定药物的特定辅助性质有关，以及（ii ）治疗可恢复表明正常血管结构的血管功能。
设计和方法：在26例未经治疗的轻度至中度原发性高血压血压计和手指BP中，心率，前臂和小腿血流量（静脉阻塞体积描记法）以及相应的血管阻力（前臂和小腿血管阻力：FVR和CVR）为lercanidipine或hydrochlorothiazide服用6个月和12个月之前和之后进行评估。还评估了局部缺血刺激（FVR（min）和CVR（min））后的血管阻力，以评估治疗对小动脉结构改变的影响。
结果：对于可叠加的BP降低，乐卡地平导致FVR和CVR的降低幅度明显大于氢氯噻嗪。同样，乐卡地平所引起的FVR（min）和CVR（min）降低也显着大于由氢氯噻嗪引起的FVR（min）和CVR（min）降低（-46.1％和-40.9％比-22.5％和-19.9％，p均<0.01）。但是，FVR（最小值）和CVR（最小值）仍然高于10个年龄匹配的血压正常个体中的FVR（最小值）。
结论：这些数据提供了证据，与氢氯噻嗪相比，乐卡地平可能通过其“辅助”特性支持更大程度地消退与高血压相关的血管结构变化。然而，乐卡地平不能恢复“正常”的血管结构，从而提示血管肥大只是部分可逆的现象。

BACKGROUND & AIMS: :The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination. Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride.

背景与目标： ：本研究的目的是单独和组合使用聚环氧乙烷和不同粘度等级的羟丙基甲基纤维素来开发和评估盐酸乐卡地平的口腔粘膜粘膜控释片剂。研究了聚合物类型，比例和组合对制剂的药物释放速率，释放机理和粘膜粘附强度的影响。通过直接压制制备颊粘膜粘附片剂，并对其含量均匀性，重量变化，易碎性，表面pH，厚度和释放机理进行表征。为了估计生物利用度的相对提高，在兔子中评估了一种优化的制剂。此外，还评估了安慰剂片剂在人类受试者中的可接受性。结果表明设计好的片剂具有可接受的物理特性，具有良好的含量均匀性和最小的重量变化。发现药物释放和粘膜粘附强度取决于聚合物类型，比例和粘度。使用聚环氧乙烷制备的制剂具有最大的粘膜粘附力。发现大多数制剂的释放机制是异常的非菲克式的。在兔子中对选定制剂的体内研究表明，相对于口服给药的药物，盐酸乐卡地平的生物利用度显着提高。此外，在人类对安慰剂制剂的可接受性研究中，设计的片剂在颊粘膜上粘附良好超过4小时，而不会引起任何不适。可以得出结论，所设计的颊粘膜控释片剂具有克服目前与盐酸乐卡地平市售制剂相关的口服生物利用度差和不稳定的潜力。

BACKGROUND & AIMS: :In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.

背景与目标： ：在所有实际的临床指南中，二氢吡啶类钙通道阻滞剂（CCB）属于推荐的用于治疗原发性高血压的一线抗高血压药物。最近的几项大型临床试验已经证实，它们不仅可以降低血压，而且可以降低具有正常或高心血管风险特征的高血压患者的心血管发病率和死亡率。在诸如ALLHAT，VALUE或ASCOT的临床试验中，基于氨氯地平的疗法在降低血压方面至少有同等效果（虽然效果不佳），有时在预防目标器官损伤方面比基于使用氨氯地平的降压策略更有效。利尿剂，β-受体阻滞剂和肾素-血管紧张素系统的阻滞剂。包括氨氯地平在内的第一代和第二代CCB的主要临床副作用之一是周围水肿的发展。通过将CCB与肾素-血管紧张素系统的阻滞剂联合使用，可以显着降低腿部浮肿的发生率。现在，该策略导致了氨氯地平和血管紧张素II受体拮抗剂的几种固定剂量组合的开发。降低水肿发生率的另一种方法是使用第三代CCB，例如lercanidipine。确实，尽管尚未对该化合物进行重大临床试验，但临床研究表明，lercanidipine和amlodipine具有相当的降压功效，但接受lercanidipine的患者外周水肿明显减少。在某些国家/地区，乐卡地平现在可以与ACE抑制剂一起以单药形式使用，从而进一步提高了其疗效和耐受性。

BACKGROUND & AIMS: :The dihydropyridine calcium channel blocker lercanidipine and the ACE inhibitor enalapril are frequently used in the treatment of hypertensive patients. In April 2007, a fixed-dose combination of the two drugs was approved in Germany for the treatment of patients not responding to monotherapy. It is expected that the drug will soon be available in the other European Union markets. In this review the present literature is summarized. Two doses will be available with 10 mg lercanidipine each and 10 or 20 mg enalapril. The medication should be taken once daily, optimally =15 minutes before a meal and the consumption of grapefruit juice should be avoided. The fixed-dose combination of the two drugs has a stronger blood pressure-lowering effect than monotherapy with 20 mg enalapril or 10 mg lercanidipine. The combination is well tolerated and few patients stopped the treatment because of side effects. As expected, the most common side effects reported are cough, peripheral edema, flushing, dizziness and vertigo, occurring in 1-5% of patients. This new fixed-dose combination is a useful adjunct to the present treatment and should increase compliance and help reduce hypertension-related costs.

背景与目标： ：二氢吡啶类钙通道阻滞剂乐卡地平和ACE抑制剂依那普利常用于高血压患者的治疗。 2007年4月，这两种药物的固定剂量组合在德国获准用于治疗对单一疗法无反应的患者。预计该药物将很快在其他欧盟市场上销售。在这篇综述中，对现有文献进行了总结。两剂将分别含10毫克lercanidipine和10或20毫克依那普利。药物应每天服用一次，最好=饭前15分钟，并且应避免食用葡萄柚汁。与20 mg依那普利或10 mg lercanidipine的单药治疗相比，两种药物的固定剂量组合具有更强的降血压作用。该组合耐受性好，几乎没有患者因副作用而停止治疗。与预期的一样，所报告的最常见的副作用是咳嗽，周围水肿，潮红，头晕和眩晕，发生于1％至5％的患者中。这种新的固定剂量组合是目前治疗的有用辅助手段，应增加依从性并有助于减少高血压相关的费用。