Molecular interaction between lacidipine and biological membranes

Abstract
To examine the molecular basis for the unique pharmacokinetics of lacidipine by defining interactions between lacidipine and biological membranes, which may explain the long clinical half-life of this calcium channel antagonist. Radiotracer analysis was used to determine the membrane partition coefficient and washout kinetics of lacidipine with membranes of different composition. Small-angle X-ray diffraction with angstrom resolution was used to determine the location of lacidipine in membranes. Lacidipine had a high membrane partition coefficient, which decreased as cholesterol in the membrane increased, and a slow rate of membrane washout. The drug was found deep within the membrane's hydrocarbon core, which was consistent with the other membrane drug parameters. Lacidipine's location and interaction within membranes may provide a longer duration of therapeutic action and can explain the unique pharmacokinetics of this drug.