THE MOLECULAR-BASIS FOR LACIDIPINES UNIQUE PHARMACOKINETICS - OPTIMALHYDROPHOBICITY RESULTS IN MEMBRANE INTERACTIONS THAT MAY FACILITATE THE TREATMENT OF ATHEROSCLEROSIS

Membrane-active drugs can be characterized by direct measurements of t heir membrane partition coefficients, washout rates from membranes, an d washin rates into membranes. There appears to be a correlation betwe en the duration of action of such membrane-active drugs and the membra ne partition coefficient in conjunction with the washout rate. Lacidip ine has a high membrane partition coefficient compared to other 1,4-di hydropyridine calcium-channel antagonists and a slow washout rate from membranes. Clinically, it also exhibits an extended duration of actio n. This control at the membrane molecular level may provide an optimal pharmacokinetic profile for lacidipine in the treatment of hypertensi on. In addition, these same properties may be important for lacidipine as an antiproliferative agent in the treatment of atherosclerosis.