Lercanidipine: Short Plasma Half-Life, Long Duration of Action

Abstract

Calcium-channel antagonist drugs of the 1,4-dihydropyridine (DHP) type bind to the L-type calcium channel. Not only are these drugs amphiphilic, but new molecular designs have become increasingly lipophilic and can readily transport across cell membranes, accessing both hydrophilic and hydrophobic environments, even though they have also become more soluble in the membrane bilayer. This biophysical understanding appears not only to define the molecular pathways for drug binding to the calcium channel receptor but also to explain differences in the overall clinical pharmacokinetics observed for different drugs in this class. The pharmacokinetic profile of calcium antagonists, although influenced to some degree by interactions with their target calcium-channel receptor, appears to be largely dictated by their interactions with the cell membranes at the molecular level. Most recently, this class of drugs has evolved from a drug such as amlodipine, with a long duration of action related to prolonged plasma half-life, to lercanidipine which has the shortest plasma half-life relative to its intrinsically long duration of action.