Comparative binding of two closely related dihydropyridines (isradipine and darodipine) to serum proteins and erythrocytes.
The binding of the two drugs isradipine and darodipine, chemically related to dihydropyridines and potent calcium channel blockers, was studied in vitro to isolated plasma proteins, erythrocytes and human serum. The two drugs were strongly bound to serum proteins (up to 97%), mainly to human serum albumin (HSA), alpha 1-glycoprotein (AAG) and lipoproteins (VLDL, LDL and HDL). Their bindings to AAG were saturable with high affinity constants (isradipine 498,000 M-1, darodipine = 155,000 M-1; n = 1). The binding of these drugs to HSA, VLDL and HDL was unsaturable, but it was saturable on LDL. In blood the drugs partitioned in erythrocytes, 16% for isradipine and 14.8% for darodipine.
Pinquier
J L
JL
Département de Pharmacologie, Faculté de Médecine, Université Paris XII, Créteil, France.
Urien
S
S
Lemaire
M
M
Chaumet-Riffaud
P
P
Tillement
J P
JP
D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000097:blood*; D004095:Dihydropyridines / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D017275:Isradipine; D008074:Lipoproteins / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood; D011725:Pyridines / Q000097:blood*; D005719:gamma-Globulins / Q000378:metabolism
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008074:Lipoproteins; D011725:Pyridines; D005719:gamma-Globulins; D009543:Nifedipine; C034600:darodipine; D017275:Isradipine