Aim: 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.
Methods: 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.
Results: 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.
Conclusions: Lacidipine's location and interaction within membranes may provide a longer duration of therapeutic action and can explain the unique pharmacokinetics of this drug.
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