General treatment of competitive binding as applied to the potentiometric ion probe technique: application to the interaction of nonsteroidal anti-inflammatory drugs with bovine serum albumin.
The binding of naproxen, ketoprofen, phenylbutazone, salicylic acid, azapropazone, and indobufen to bovine serum albumin was studied by applying the potentiometric ion probe technique. An ion-selective electrode for the ion probe 1-anilino-8-naphthalene-sulfonate was utilized for the purposes of this study. A modified site-oriented competitive binding model was used for the estimation of the drugs' binding parameters, considering different number of binding sites on the competing binding class(es) for the probe and the drug. Calculations were based exclusively on the concentration data of the free probe. The model's ability for accurate estimations of binding parameters was evaluated by simulation studies. The following values of binding parameters were found at 25 degrees C for the drugs under study; naproxen, n1 = 9.1, k1 = 9.4 x 10(5) M-1; ketoprofen, n1 = 8.8, k1 = 10.8 x 10(5) M-1; phenylbutazone, n1 = 3.2, k1 = 1.4 x 10(5) M-1; salicylic acid, n1 = 2.6, k1 = 1.8 x 10(5) M-1, n2 = 21.5, k2 = 1.0 x 10(4) M-1; azapropazone, n1 = 0.5, k1 = 7.8 x 10(5) M-1, n2 = 26.3, k2 = 1.9 x 10(4) M-1; indobufen, n1 = 5.8, k1 = 5.8 x 10(5) M-1, n2 = 19.9, k2 = 3.8 x 10(5) M-1, where ni the number of binding sites of the i class and ki the corresponding association constant.
Angelakou
A T
AT
Department of Pharmacy, University of Athens, Panepistimiopolis, Greece.
Sideris
E E
EE
Valsami
G N
GN
Koupparis
M A
MA
Macheras
P E
PE
D000817:Anilino Naphthalenesulfonates; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D003198:Computer Simulation; D007202:Indicators and Reagents; D008024:Ligands; D011199:Potentiometry; D011485:Protein Binding; D012044:Regression Analysis; D012710:Serum Albumin, Bovine / Q000737:chemistry*
D000817:Anilino Naphthalenesulfonates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D008024:Ligands; D012710:Serum Albumin, Bovine