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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lercanidipine is a new 1,4-dihydropyridine derivative with potent, long-lasting and vascular-selective calcium entry blocking activity. Animal models of hypertension have shown lercanidipine to be potent, with a slow rate of onset and long lasting action and to have minimal or no effects on cardiac contractility. There was no evidence of tolerance after repeated oral treatment, and no effects were found on the autonomic nervous, central nervous, gastrointestinal or respiratory systems at antihypertensive doses. In man, lercanidipine is well absorbed after oral administration, with peak plasma levels occurring approximately 1.5 - 3 h after dosing. The drug is subject to extensive hepatic first pass metabolism with an elimination half-life of 2 - 5 h. With a more sensitive method, a mean terminal elimination half-life of 8 - 10 h was defined. Despite this short plasma half-life the drug has a long duration of action, most likely due to the high lipophilicity of lercanidipine and its partitioning in to the lipid bilayer of cell membranes, followed by diffusion to the receptor binding site. The efficacy of lercanidipine has been established in extensive clinical trials with comparison to both placebo and standard well-established antihypertensive therapies. These trials confirmed the efficacy of lercanidipine and its long duration of action which renders it suitable for once daily administration. Tolerability was good in all studies: the adverse event profile was comparable to that of placebo at lower doses, with a low incidence of palpitations and ankle oedema. Lercanidipine is a recently introduced example of a lipophilic and vasoselective dihydropyridine calcium antagonist which is an effective antihypertensive drug with a slow onset and long duration of action; it is associated neither with reflex tachycardia nor cardio-depressant activity.
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PMID:Lercanidipine: a novel lipophilic dihydropyridine calcium antagonist with long duration of action and high vascular selectivity. 1599 5

1. The present study investigates the vasoselectivity of lercanidipine (LER), a 1,4-dihydropyridine calcium channel blocker, compared with amlodipine (AML) and nifedipine (NIF) in human cardiovascular tissue. Experiments were performed either in human left ventricular failing myocardium (orthotopic heart transplants) or in isolated right atrial trabeculae and isolated vessel preparations of arteria mammaria obtained from patients undergoing aortocoronary bypass operation. 2. The obtained rank order for the L-type Ca2+ channel affinity in human tissue was LER > NIF >or= AML. Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae. 3. The vasorelaxant potency of LER (IC50 0.5 nmol/L) and AML (IC50 0.8 nmol/L) was similar and significantly increased compared with that of NIF (IC50 5.9 nmol/L) in arteria mammaria preparations of the very same patients. 4. The following rank order was obtained for vasoselectivity: LER (260) < AML (60) < NIF (0.6). 5. The pharmacological effects of LER and AML were still present 2 h after drug washout. 3. Lercanidipine is characterized by a high vasoselectivity and a prolonged interaction with the L-type calcium channel in human cardiovascular tissue This may be advantageous, especially in the treatment of patients with arterial hypertension.
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PMID:Increased vascular selectivity and prolonged pharmacological efficacy of the L-type Ca2+ channel antagonist lercanidipine in human cardiovascular tissue. 1617 26

The photostability of lercanidipine, a dihydropyridine calcium-channel blocker used in the treatment of the hypertension, was studied. Drug substance and its solutions and formulations were exposed to UV-A radiations (solar simulator) and the photodegradation process was monitored by UV spectrophotometry, HPLC and HPLC-mass spectrometry. The effect of the solvent (ethanol and ethanol/PBS 1:1 v/v) on the photodegradation pathway and kinetic was evaluated. Lercanidipine and its photodegradation products were separated by a selective reversed-phase HPLC method and the main photoproducts were characterized by HPLC-MS/MS analysis, using an electrospray ionization source (ESI) and an ion trap analyzer. Photochemical reactions, involved in the photodegradation of lercanidipine, include aromatisation of the dihydropyridine moiety, formation of nitrosoderivatives and N-dealkylation in the side chain. The developed stability-indicating HPLC method was then applied to the quality control of commercially available lercanidipine formulations (tablets).
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PMID:Investigation on the photochemical stability of lercanidipine and its determination in tablets by HPLC-UV and LC-ESI-MS/MS. 1637 7

To determine whether the antihypertensive effectiveness of lercanidipine was independent of the different cardiovascular risk levels. Patients with treated or untreated mild-to-moderate essential hypertension were included in a multicentre, prospective, non-comparative, open-label study. Patients received lercanidipine (10 mg/day, uptitrated to 20 mg/day) during 6 months. A total of 3175 patients, age 63 +/- 10 years, 51% women, were included. The cardiovascular risk was low in 237 patients, medium in 1396, high in 722, and very high in 820. At baseline, blood pressure (BP) was 159.5 +/- 11.7/95.2 +/- 7.4 mmHg. BP was progressively higher according to increase in cardiovascular risk. After 6 months of treatment, BP was 136.0 +/- 9.7/79.7 +/- 6.8 mmHg. The decrease in systolic BP and diastolic BP at each follow-up visit compared with baseline was statistically significant both in the intergroup and intragroup comparisons (p < 0.001). Mean decreases of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -18.5/-13.8 mmHg in the low risk group, -23/-15.2 mmHg in the medium risk group, -24.4/-16.1 mmHg in the high risk group, and -27.4/-17.4 mmHg in the very high risk group. Most frequent side effects were oedema (5.1%), headache (3.3%), flushes (2.5%), and asthenia (1%). Only 1.7% of patients discontinued antihypertensive medication because of adverse events. Tolerability of lercanidipine was independent of the cardiovascular risk group. Lercanidipine was effective and well-tolerated in patients with mild-to-moderate hypertension in the daily practice. The effectiveness and safety of the drug were independent of the degree of cardiovascular risk.
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PMID:Lercanidipine is an effective and well tolerated antihypertensive drug regardless the cardiovascular risk profile: The LAURA study. 1707 34

Systemic hypertension is a major global problem contributing to enormous disease burden, premature morbidity and mortality. A substantial majority of hypertensive patients require long-term drug therapy for appropriate blood pressure control. Although there are many classes of antihypertensive drugs for clinical use, calcium channel blockers (CCBs) have a special role in the management of hypertension owing to their well established safety and efficacy among the CCBs; the dihydropyridines (DHPs) are recognized for their predictable efficacy and dependability to achieve the recommended target goals of treatment. The older DHPs, such as nifedipine, felodipine and amlodipine, can cause bothersome side effects, such as ankle edema. The new-generation lipophilic DHP CCBs, such as lercanidipine, offer an advantage of less frequent occurrence of ankle edema. Furthermore, lercanidipine (in contrast to older DHPs) exerts favorable cardiorenal effects. Lercanidipine administered alone or in combination with other antihypertensive drugs represents a useful treatment option for efficient blood pressure control without causing significant adverse effects.
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PMID:Hypertension, possible vascular protection and lercanidipine. 1717 95

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 <or=5.2% and peripheral oedema in <or=1.5% of lercanidipine/enalapril recipients.
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PMID:Fixed-dose combination lercanidipine/enalapril. 1720 66

Lercanidipine is a lipophilic, dihydropyridine calcium antagonist with a long receptor half-life. Its slow onset of action helps to avoid reflex tachycardia associated with other dihydropyridines (DHPs). It produces even and sustained blood pressure lowering with once-daily dosing. It has equivalent antihypertensive efficacy to many other agents and is effective as initial monotherapy or in combination. Efficacy has been demonstrated in elderly as well as younger patients and also in the presence of other risk factors. Lercanidipine is well tolerated with DHP-associated adverse effects occurring early in treatment. The incidence of pedal edema and subsequent withdrawals has been found to be lower with lercanidipine than with amlodipine or nifedipine gastrointestinal transport system. Preclinical and preliminary clinical findings suggest lercanidipine may have beneficial effects on atherosclerosis and left ventricular hypertrophy. The efficacy and tolerability profiles of lercanidipine make it a suitable choice for treating hypertension in a wide range of affected patients.
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PMID:Lercanidipine in hypertension. 1731 3

The study was undertaken to determine the effect of treatment with the dihydropyridine-type calcium antagonist lercanidipine on the renal vasculature in Cohen-Rosenthal diabetic hypertensive rats, a genetic model of hypertension associated with type 2 diabetes mellitus. Eight animals were given a daily oral dose of 3 mg/kg lercanidipine in drinking water for 8 weeks, and 6 control animals received no treatment. The effects on blood pressure, glucose level, and kidney microanatomy were evaluated. Lercanidipine reduced systolic blood pressure and glucose level. In the control group small arteries and glomerular arterioles exhibited wall thickening and luminal narrowing. Lercanidipine administration prevented the changes in small-sized arteries and glomerular arterioles. The glomerular changes observed in the untreated Cohen-Rosenthal diabetic hypertensive rats were not seen in the lercanidipine-treated animals. Lercanidipine also had beneficial effects on the renal vasculature, suggesting that the compound may be considered for treating hypertension associated with diabetes.
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PMID:Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats. 1756 85

Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224+/-12 versus 183+/-11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P<0.01) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of 2K-1C rats (all P<0.05). Lercandipine attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C-induced increases in oxidative stress (both P<0.001). While hypertension-induced significant aortic wall hypertrophy and approximately 9-fold increases in the ratio of MMP-2/TIMP-2 mRNA expression (both P<0.05), lercandipine did not affect these changes. These results suggest that lercanidipine produces antihypertensive effects and reverses the endothelial dysfunction associated with 2K-1C hypertension, probably through mechanisms involving antioxidant effects leading to lower MMP-2 activation.
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PMID:Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats. 1863 78

Despite the development of many effective antihypertensive drugs, target blood pressures are reached in only a minority of patients in clinical practice. Poor adherence to drug therapy and the occurrence of side effects are among the main reasons commonly reported by patients and physicians to explain the poor results of actual antihypertensive therapies. The development of new effective antihypertensive agents with an improved tolerability profile might help to partly overcome these problems. Lercanidipine is an effective dihydropyridine calcium channel blocker of the third generation characterized by a long half-life and its lipophylicity. In contrast to first-generation dihydropyridines, lercanidipine does not induce reflex tachycardia and induces peripheral edema with a lower incidence. Recent data suggest that in addition to lowering blood pressure, lercanidipine might have some renal protective properties. In this review we shall discuss the problems of drug adherence in the management of hypertension with a special emphasis on lercanidipine.
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PMID:Patient adherence and the choice of antihypertensive drugs: focus on lercanidipine. 1933 29


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