Lercanidipine: a review of its use in hypertension

Lercanidipine is a vasoselective dihydropyridine calcium antagonist which causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug and as such has a slower onset and longer duration of action than a number of other calcium antagonists. Preclinical evidence suggests that lercanidipine has antiatherogenic potential and it may also protect against end-organ damage. In well controlled clinical studies, once daily administration of lercanidipine 10 or 20mg effectively reduced blood pressure (BP) compared with placebo in patients with mild to moderate hypertension without affecting heart rate. Response rate (percentage of patients with diastolic BP < or =90mm Hg or reduced by > or =10mm Hg from baseline) ranged from 50 to 66% with lercanidipine 10 mg/day and up to 86% with lercanidipine 20 mg/day. The drug had a long duration of action: clinical measurements for diastolic BP yielded a trough/peak ratio of >0.8 for both lercanidipine dosages in 1 study. Comparative trials, either published in full or as abstracts, found lercanidipine 10mg once daily for > or =4 weeks to be at least as effective as atenolol 50mg once daily, candesartan cilexetil 16 mg/day, captopril 25mg twice daily, enalapril 20 mg/day, hydrochlorothiazide 12.5mg once daily, irbesartan 150 mg/day and slow release nifedipine 20mg twice daily in patients with mild to moderate hypertension. In addition, lercanidipine 20 mg/day was as effective as amlodipine 10 mg/day. Lercanidipine is effective in the treatment of elderly patients (aged 60 to 85 years) with mild to moderate essential hypertension and in those with isolated systolic hypertension. In addition, monotherapy with lercanidipine 20 or 40 mg/day has shown efficacy in patients with severe hypertension, and add-on therapy helped control BP in a large proportion of patients with severe hypertension not responding sufficiently to beta-blockers, diuretics or ACE inhibitors. Unpublished data indicate that the drug reduces blood pressure in patients with type 2 (non-insulin-dependent) diabetes mellitus, without adversely affecting glucose homeostasis. Lercanidipine was well tolerated in clinical trials, with most treatment-related adverse events typical of dihydropyridine calcium antagonists, namely headache, flushing, dizziness and ankle oedema. CONCLUSIONS: Lercanidipine is an effective and well tolerated once daily antihypertensive agent in patients with mild to moderate hypertension. In addition, the drug may reduce BP when used as monotherapy in patients with severe hypertension or when used adjunctively in patients with resistant hypertension. Importantly, lercanidipine appears to be at least as effective and well tolerated as other commonly used antihypertensive agents. The drug therefore represents a useful therapeutic option in the management of patients with hypertension and will be particularly useful in patients not responding to, or intolerant of, antihypertensive agents from other drug classes.     

乐卡地平与培哚普利联合治疗轻中度高血压疗效及安全性观察

目的评价乐卡地平与培哚普利小剂量单独治疗和联合治疗轻度原发性高血压的疗效及安全性。方法 180例轻度原发性高血压患者随机分成联合治疗组（A组）和单用乐卡地平组（B组）和单用培哚普利组（C组）。A组服用培哚普利2 mg·d^-1＋乐卡地平5 mg·d^-1;B组服用乐卡地平10 mg·d^-1;C组服用培哚普利4 mg·d^-1。分别观察三组治疗后4、8、12周后降压效果及安全性。结果联合治疗组第4周开始,血压达标率及血压下降幅度均优于单药治疗组,三组间差异有统计学意义（P〈0.05）。联合治疗组治疗期间不良事件发生4例,明显低于单药治疗组（乐卡地平组7例,培哚普利组19例）,差异有显著性（P〈0.05）。结论乐卡地平与培哚普利联合应用可明显增加降压幅度和降压速度、提高降压有效率,两药小剂量联合可减少药物不良反应发生率。     

Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension

Increased levels of metalloproteinase (MMP)-9 have been shown in hypertensive patients. Lercanidipine is a calcium channel blocker with antioxidant actions. We examined whether lercanidipine produces antioxidant effects and reduces MMP-9 activity in hypertensive patients in a placebo-controlled, crossover, single-blinded design study including 18 healthy volunteers (control group), and 14 hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus. Hypertensive patients were randomized to treatment with placebo (15 days) or lercanidipine 20 mg/d (15 days). Arterial blood pressure was evaluated with ambulatory blood pressure monitoring. Plasma thiobarbituric acid reactive species (TBA-RS) levels were measured to assess oxidative stress, and plasma MMP-2 and MMP-9 were assayed by gel zymography before and after treatment with placebo or lercanidipine. Plasma concentrations of tissue inhibitor of metalloproteinases (TIMP)-1 were measured by ELISA. Lercanidipine reduced mean arterial pressure by 7% in hypertensive patients without diabetes (P < 0.05), but not in hypertensive patients with diabetes. It significantly decreased plasma TBA-RS levels in hypertensive patients without and with diabetes (95% confidence interval [CI], -26 to -46%, P = 0.048, and -22 to -33%, P = 0.036, respectively). In addition, lercanidipine decreased activated MMP-9 in hypertensive patients without and with diabetes (95% CI, -19 to -47%, P = 0.047, and -80 to -96%, P = 0.010, respectively). No effects were seen on MMP-2. No significant differences or changes in plasma TIMP-1 concentrations were found. Therefore, we demonstrate for the first time that lercanidipine consistently decreased MMP-9 activity and reduced oxidative stress in hypertensive patients, thus suggesting a mechanism probably involved in the pleotropic actions of lercanidipine.     

Fixed-dose combination lercanidipine/enalapril

Lercanidipine, a dihydropyridine calcium channel blocker, and enalapril, an ACE inhibitor, are established antihypertensive agents. A fixed-dose tablet formulation of lercanidipine/enalapril is approved in Germany for the treatment of hypertension in patients not responding to monotherapy. Lercanidipine/enalapril 10mg/10mg once daily significantly reduced sitting diastolic blood pressure and sitting systolic blood pressure, relative to lercanidipine 10mg once daily, in a 12-week, randomised, double-blind trial in patients with mild to moderate hypertension who had previously not responded to 4 weeks' treatment with lercanidipine. In a similarly designed trial, lercanidipine/enalapril 10mg/20mg once daily was significantly more effective than enalapril 20mg once daily in hypertensive patients who had previously not responded to enalapril monotherapy. Fixed-dose lercanidipine/enalapril was generally well tolerated, with a tolerability profile similar to that of either of the individual drugs alone or placebo. Cough was reported in 相似文献   

Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2.

Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.     

罗格列酮与二甲双胍对2型糖尿病患者血压的影响

目的:探讨罗格列酮和二甲双胍对2型糖尿病患者血压的影响及其作用机制。方法:58例2型糖尿病患者,随机分成2组,分别口服罗格列酮(4～8mg,qd)和二甲双胍(250～500mg,tid)治疗,在试验期间不使用其它对血压有影响的药物。观察治疗前后两组患者收缩压(SBP)、舒张压(DBP)、空腹血糖(FBG)、餐后2h血糖(PBG)、空腹血浆胰岛素(FINS)、餐后2h血浆胰岛素(PINS)水平,共观察12周,计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(IR)。结果:罗格列酮和二甲双胍治疗后收缩压和舒张压均有明显下降(P<0.05);罗格列酮组SBP和DBP降低幅度均大于二甲双胍组(P<0.05);两组病例FBG、PBG、FINS和PINS均明显降低(P<0.05);两组胰岛素敏感性的指标ISI升高(P<0.05),胰岛素抵抗的指标IR下降(P<0.05),罗格列酮组ISI升高和IR下降幅度大于二甲双胍组(P<0.05)。结论:罗格列酮和二甲双胍在改善胰岛素抵抗、提高胰岛素敏感指数的同时,具有降低血压的作用,罗格列酮的作用优于二甲双胍。     

Felodipine extended release in mild to moderate hypertension

A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release (ER) formulation given once daily as monotherapy. Doses of 5 mg, 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension. All antihypertensive medication was discontinued on entering a 4-week placebo run-in period. If, at the end of the run-in period, supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg, patients were randomly allocated to double-blind treatment with felodipine, 5 mg, 10 mg or 20 mg, or placebo, to be taken once daily for 4 weeks. Supine and standing blood pressure, heart rate and body weight were measured every 2 weeks during the trial. Assessments were made 24 hours after intake of the study drug. Adverse events were recorded at each review. Over the 4-week treatment period, a dose-related decrease in supine diastolic blood pressure was observed, this reduction occurring already during the first 2 weeks of active treatment. In the placebo group and the felodipine 5 mg, 10 mg and 20 mg groups, supine blood pressure (systolic/diastolic) decreased by 7/6 mmHg, 9/8 mmHg, 12/10 mmHg and 14/11 mmHg, respectively. Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo. Standing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

贝那普利联合乐卡地平治疗原发性高血压的疗效与安全性

目的评价贝那普利联用乐卡地平治疗原发性高血压的疗效和安全性。方法将原发性轻中度高血压患者80例随机分为A组(贝那普利10 mg/乐卡地平10 mg)和B组(贝那普利10 mg)。治疗第4周时坐位舒张压(DBP)仍≥90 mmHg的患者,贝那普利治疗剂量加倍,继续治疗4周,DBP<90 mmHg则维持原剂量,继续治疗4周。结果治疗4周时,A组收缩压(SBP)下降幅度显著大于B组(P<0.05);8周时,A组血压下降幅度显著大于B组(P<0.05)。治疗4、8周时,两组达标率分别为82.1%、59.5%(P<0.05);87.2%、67.6%(P<0.05)。两组不良事件发生率差异无统计学意义。结论贝那普利/乐卡地平联合治疗原发性高血压,可显著降低血压,提高降压达标率,两药联合安全有效。     

Once- and twice-daily nitrendipine in patients with hypertension and noninsulin-dependent diabetes

One hundred and six patients with uncomplicated mild to moderate essential hypertension received nitrendipine 10 mg twice a day or 20 mg once a day in a double-blind, randomized design. At the end of the dosing interval, supine and standing blood pressures were lowered 6/4 and 6/3 mm Hg respectively with the former regimen, and 2/3 mm Hg with the latter. In 10 patients, blood pressure variability through the dosing interval was not increased by nitrendipine 10 mg twice daily, but in another 10, 20 mg daily increased the variability by 28% compared to placebo. Significantly more patients had adverse effects with 20 mg daily than 10 mg twice daily; and both regimens caused more side effects than placebo. In 20 patients, serum glucose levels did not change significantly during treatment with nitrendipine, but in 10 of those with noninsulin-dependent diabetes, the range of maximum plasma insulin in response to a high-carbohydrate meal was 7 times as great during treatment with nitrendipine as it was during treatment with placebo. Nitrendipine lowers blood pressure when given once or twice daily, but twice-daily administration appears to be better tolerated.     

应用动态血压监测评价培哚普利治疗原发性高血压的降压疗效

目的：应用动态血压监测（ABPM）评估培哚普利（Perindopril）对轻、中度原发性高血压（EH）病人的24h降压效果。方法：轻、中度EH病人36例,服用2周安慰剂,坐位舒张压仍在95ˉ114mmHg者给与培哚普利4mg/d治疗8周。及治疗2、4、6、8周末测诊室血压,于服安慰剂末及治疗8周末应用ABPM。结果：培哚普利治疗8周,降压总有效率为83.3%;24h各时点血压均较治疗前显著下降（P＜0.01）不伴有心率及血压昼夜节律的改变;降低收缩压和舒张压的谷／峰值分别为80.6%和86.7%。结论：培哚普利能平稳、有效的控制EH病人24h血压,且病人总体耐受良好。     

Lercanidipine : a review of its efficacy in the management of hypertension

Lercanidipine (Zanidip) is a vasoselective dihydropyridine calcium channel antagonist that causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug that exhibits a slower onset and longer duration of action than other calcium channel antagonists. Furthermore, lercanidipine may have antiatherogenic activity unrelated to its antihypertensive effect.In two large, nonblind, noncomparative studies involving approximately 16 000 patients with mild-to-moderate hypertension, systolic blood pressure (BP) [SBP] and diastolic BP (DBP) were significantly reduced after 12 weeks' treatment with lercanidipine 10-20 mg/day. Furthermore, in the largest study, 64% of patients were responders (DBP <90 mm Hg) after 12 weeks of treatment and an additional 32% had their BP normalised (BP <140/90 mm Hg). In comparative trials, lercanidipine 10-20 mg/day was as effective as nifedipine slow release (SR) 20-40 mg twice daily, amlodipine 10 mg/day, felodipine 10-20 mg/day, nifedipine gastrointestinal therapeutic system (GITS) 30-60 mg once daily or verapamil SR 240 mg/day at reducing SBP and DBP in patients with mild-to-moderate hypertension after 2-16 weeks of therapy. In addition, 4 weeks of lercanidipine therapy (10 mg/day) was as effective as captopril 25mg twice daily, atenolol 50 mg/day or hydrochlorothiazide 12.5 mg/day.Lercanidipine 5-30 mg/day effectively decreased BP in elderly patients (aged >60 years) with mild-to-moderate hypertension or isolated systolic hypertension to the same extent as amlodipine 5-10 mg/day, nifedipine GITS 30-60 mg/day or lacidipine 2-4 mg/day after 24-26 weeks of therapy. In addition, a limited number of studies suggest that lercanidipine may have antihypertensive efficacy in patients with severe or resistant hypertension, in hypertensive patients with type 2 diabetes mellitus and in postmenopausal women with mild-to-moderate essential hypertension. Lercanidipine is well tolerated, with most treatment-emergent events related to vasodilation. Common adverse events included headache, flushing and peripheral oedema. Importantly, the incidence of vasodilatory oedema was significantly lower in patients receiving lercanidipine than in those receiving some other calcium channel antagonists. CONCLUSION: Once-daily lercanidipine is an effective and well tolerated antihypertensive agent in patients with mild-to-moderate hypertension.     

高血压合并糖尿病患者血糖对血压及内皮功能的影响

目的通过对高血压合并2型糖尿病患者血糖水平的控制,探讨不同血糖水平对降压疗效及内皮功能的影响。方法选择住院和门诊高血压合并2型糖尿病患者68例,根据高血压和2型糖尿病治疗指南选择降压和降糖方案,记录患者治疗过程中不同血糖水平时的降压疗效,同时检测治疗开始与结束时的空腹血糖(FPG)、血浆内皮素(ET-1)及尿清蛋白排泄率(Urinary albumin excretion rate,UAER)。结果随着治疗过程中血糖水平的逐渐改善,血压达标人数明显增加。经过4～6周的降糖治疗,血糖接近达标(6.1～6.9mmol/L)和达标(<6.1mmol/L)时,血压达标率分别为82.35%和95.59%,和血糖≥7.0mmol/L(血压达标率51.47%)及≥7.8mmol/L(血压达标率27.94%)水平相比有显著性差异;同时,治疗前后患者FPG、血浆ET-1及UAER均明显下降。结论高血压合并2型糖尿病患者血糖水平与降压疗效关系密切,良好的血糖控制有利于血压的治疗,从而改善内皮功能,更好地预防靶器官损害,防止并发症的发生。     

Metabolic effects of long-term angiotensin-converting enzyme inhibition with fosinopril in patients with essential hypertension: relationship to angiotensin-converting enzyme inhibition

Fifty patients with mild to moderate essential hypertension were randomized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to these 16 weeks there was a placebo wash-out period of 2–6 weeks. Blood pressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and after 4 and 16 weeks. Blood lipid status was evaluated at baseline and 16 weeks.The insulin sensitivity index (M/I) increased by 12% during the prolonged placebo period, and subsequently decreased by 12% during treatment with atenolol in that group. A post-hoc analysis of covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry over effects from previous anti-hypertensive treatment. Fosinopril increased glucose disappearance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 at baseline) but had no effect on insulin sensitivity. The change in insulin sensitivity and serum triglycerides during treatment with fosinopril was related to angiotensin-converting enzyme inhibition in serum.In conclusion, carry-over effects from previous anti-hypertensive medication were indicated in this study, probably because of an insufficient wash-out period in many patients. Therefore, 4 weeks of placebo wash-out in all patients is advisable in this kind of investigation.     

Felodipine ER formulation in the treatment of mild hypertension: efficacy and tolerability vs placebo.

1. Felodipine is a new calcium-antagonist dihydropyridine derivative with a high degree of selectivity for smooth muscle of arteriolar resistance vessels, as opposed to cardiac cells. 2. In this double-blind, cross-over study the antihypertensive efficacy and tolerability of the new extended release (ER) formulation of felodipine 10 mg, once daily, in patients with mild essential hypertension was evaluated. After a 4-week single-blind placebo period 28 patients (15 males; mean age 48 +/- 12 years) were randomized to receive felodipine 10 mg ER once daily or placebo for 4 weeks and the alternative treatment for a further 4 weeks. Supine blood pressure and heart rate were measured in the out-patients department every 2 weeks, 22-24 h after the last drug administration. 3. Felodipine 10 mg ER induced a significant reduction in blood pressure in comparison with placebo (from 149 +/- 16/97 +/- 6 to 140 +/- 12/89 +/- 6 mm Hg). Heart rate remained unchanged. Seven patients dropped-out; five during felodipine ER administration and two during placebo. 4. A once daily dose of felodipine ER significantly reduces blood pressure in mild hypertensive patients 22-24 h after administration. It is well tolerated and the adverse events are related to its pharmacodynamic effects.     

Treatment of mild and moderate hypertension with medroxalol, an alpha- and beta-adrenergic antagonist

Medroxalol, a new antihypertensive agent with alpha- and beta-adrenoreceptor blocking properties in both animals and humans, was administered in a single-blind study for 12 weeks to 29 patients with mild and moderate hypertension (standing blood pressure: 188-130/130-100 mm Hg). After 4 weeks of placebo administration, treatment with oral medroxalol was begun. Six weeks later, half the subjects added hydrochlorothiazide, 12.5 mg twice daily, to medroxalol for an additional 6 weeks, and the other half added placebo. During the final 4-week period medroxalol, but not hydrochlorothiazide, was discontinued and placebo substituted. Oral medroxalol doses of 100-400 mg twice daily reduced standing diastolic pressure to less than 100 mm Hg in 21 of the 26 subjects who completed the study. Compared to the last values on placebo, mean standing blood pressure was decreased by 15.6/12.0 mm Hg during the first 6 weeks of medroxalol at mean daily doses of 388-407 mg. Addition of hydrochlorothiazide permitted some decrease in medroxalol dosage. Upon medroxalol withdrawal, blood pressure and heart rate returned toward pretreatment values, with subjects continuing on diuretic showing lower blood pressures than the untreated individuals. Tolerance to medroxalol, with or without hydrochlorothiazide, was good. Mild orthostatic dizziness was the most frequent complaint associated with therapy, but postural hypotension was not found on physical examination. Medroxalol appears to be effective and well tolerated for reducing the blood pressure of most patients with mild to moderate hypertension and may be useful for chronic oral therapy of this disease.     

Manidipine: a review of its use in hypertension.

Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40 mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in noncomparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mglday) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or moderate essential hypertension. The BP-lowering effects of the drug in patients with hypertension and type 2 diabetes mellitus or impaired glucose tolerance were not associated with any adverse metabolic effects. The effects of manidipine on UAE in this patient group remain unclear. Manidipine provides an additional treatment option for patients for whom dihydropyridine calcium antagonists are appropriate. Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in non-comparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mg/day) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or mo     

吡格列酮对2型糖尿病患者血清脂联素与胰岛素抵抗的影响

目的探讨吡格列酮对2型糖尿病患者血清脂联素水平及胰岛素抵抗的影响。方法2型糖尿病患者45例,两组年龄、性别匹配,按随机双盲法分为吡格列酮组（22例）和安慰剂组（23例）,干预治疗12周后比较其血清脂联素、游离脂肪酸（FFA）水平,同时测血糖、血压、血脂、身高、体重、腰围、臀围,计算体重指数（BMI）、腰臀比值（WHR）、空腹胰岛素（Fins）和胰岛13细胞功能（HOMA-IR）。结果治疗前两组的脂联素、游离脂肪酸水平无明显差别,经吡格列酮治疗后,患者血糖、胰岛素抵抗明显改善（P〈0．05）,血清脂联素水平显著升高（P〈0．05）,血清FFA水平下降（P〈0．05）,血清脂联素升高与FFA下降无显著相关性（P〉0．05）。结论吡格列酮除改善血糖及胰岛素抵抗外,还可使血清脂联素水平升高,FFA水平降低,提示吡格列酮可能通过降低FFA、升高脂联素水平改善2型糖尿病患者胰岛素抵抗。     

Long-term effect of tiapamil in essential hypertension

To evaluate the long-term effect of tiapamil, a new calcium antagonist, in hypertension, 20 adult patients suffering from mild to moderate hypertension were entered into a 58-week open study. In 10 patients, blood pressure returned to normal within 1-6 weeks with a daily dose of 600-900 mg tiapamil. In the remaining 10 patients, the blood pressure became normal after 8-28 weeks with a daily dose of 900-1,200 mg tiapamil. The more severe the hypertension, the higher the dose needed and the longer the time required for the blood pressure to return to normal. The overall results at the end of the 58-week treatment showed a significant decrease of the blood pressure to 142 (+/- 9)/88 (+/- 4) mmHg from a before treatment average of 166 (+/- 16)/105 (+/- 7) (p less than 0.001). There was no marked difference in the blood pressure between supine and sitting positions before or after treatment. Side effects were mild and self-limiting, with no patient being dropped from the study. Electrocardiogram (ECG) and laboratory values were not affected during the treatment with the exception of a moderate decrease in the blood glucose. Neither plasma renin activity, nor aldosterone concentration, nor serum cholesterol or triglyceride levels were altered during tiapamil administration. Tiapamil appears to be an effective and well-tolerated drug for use in mild to moderately severe hypertension.     

Efficacy of a fixed-dose combination of 40 mg penbutolol with 6 mg piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo

The antihypertensive efficacy and tolerability of a fixed-dose combination containing 40 mg penbutolol (a beta-blocking agent) and 6 mg piretanide (a diuretic) in comparison to placebo was investigated in a double-blind, crossover study in 20 patients with mild to moderate essential hypertension. After a 1-week period on placebo, patients were allocated at random to receive 1 tablet daily for 4 weeks of either the combination preparation or placebo and were then crossed over to the alternative medication for a further 4 weeks. The reduction in systolic and diastolic blood pressure both at rest, during maximal ergometric exercise and isometric word load, and also in the diurnal blood pressure profile over 24 hours was significantly greater in the group treated with the fixed-dose combination than in the placebo group. Pulse rate was also decreased to a greater extent. Mean diastolic blood pressure before exercise was reduced to normal (85.5 mmHg) after 4-weeks' treatment with the fixed-dose combination. Biochemical, haematological and urinary parameters showed no clinically relevant changes after either treatment. One patient complained of transient dizziness during treatment with the fixed-dose combination. No patient withdrew prematurely from the study because of side-effects.     

罗格列酮联合二甲双胍对非高血压2型糖尿病患者血压的影响

目的研究罗格列酮联合二甲双胍对非高血压2型糖尿病患者血压的影响。方法48例患者口服二甲双胍片1500mg／d和罗格列酮4mg／d，治疗8周。结果治疗后平均收缩压下降4．1mmHg，平均舒张压下降3．5mmHg（P〉0．05）；空腹血糖、空腹胰岛素水平治疗后均较治疗前降低（8．1±1．8vs6．5±2．1；14．6±5．9vs12．1±4．7，P〈0．05），HOMA胰岛素抵抗指数治疗后亦降低（3．6±1．5vs4．9±1．9，P〈0．05）。结论罗格列酮联合二甲双胍治疗能够有效降低血糖，改善胰岛素抵抗，但是对非高血压2型糖尿病患者降低血压的作用不明显。