Lercanidipine: a novel lipophilic dihydropyridine calcium antagonist with long duration of action and high vascular selectivity

Abstract

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.

• anti-atherosclerotic
• calcium antagonists
• calcium channel blocker
• lercanidipine
• lipophilic
• vasoselective