The molecular basis for lacidipine's unique pharmacokinetics: optimal hydrophobicity results in membrane interactions that may facilitate the treatment of atherosclerosis.
Membrane-active drugs can be characterized by direct measurements of their membrane partition coefficients, washout rates from membranes, and washin rates into membranes. There appears to be a correlation between the duration of action of such membrane-active drugs and the membrane partition coefficient in conjunction with the washout rate. Lacidipine has a high membrane partition coefficient compared to other 1,4-dihydropyridine calcium-channel antagonists and a slow washout rate from membranes. Clinically, it also exhibits an extended duration of action. This control at the membrane molecular level may provide an optimal pharmacokinetic profile for lacidipine in the treatment of hypertension. In addition, these same properties may be important for lacidipine as an antiproliferative agent in the treatment of atherosclerosis.
Herbette
L G
LG
Department of Radiology, University of Connecticut Health Center, Farmington 06030, USA.
Mason
P E
PE
Gaviraghi
G
G
Tulenko
T N
TN
Mason
R P
RP
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008566:Membranes / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine