GENERAL TREATMENT OF COMPETITIVE-BINDING AS APPLIED TO THE POTENTIOMETRIC ION PROBE TECHNIQUE - APPLICATION TO THE INTERACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH BOVINE SERUM-ALBUMIN

The binding of naproxen, ketoprofen, phenylbutazone, salicyclic acid, azapropazone, and indobufen to bovine serum albumin was studied by app lying the potentiometric ion probe technique. An ion-selective electro de for the ion probe 1-anilino-8-naphthalenesulfonate was utilized for the purposes of this study. A modified site-oriented competitive bind ing model was used for the estimation of the drugs' binding parameters , considering different number of binding sites on the competing bindi ng class(es) for the probe and the drug. Calculations v,ere based excl usively on the concentration data of the free probe. The model's abili ty for accurate estimations of binding parameters was evaluated by sim ulation studies. The following values of binding parameters were found at 25 degrees C for the drugs under study; naproxen, n(1) = 9.1, k(1) = 9.4 X 10(5) M(-1); ketoprofen, n(1) = 8.8, k(1) = 10.8 X 10(5) M(-1 ); phenylbutazone, n(1) = 3.2, k(1) = 1.4 X 10(5) M(-1); salicylic aci d, n(1) = 2.6, k(1) = 1.8 X 10(5) M(-1), n(2) = 21.5, k(2) = 1.0 X 10( 4) M(-1); azapropazone, n(1) = 0.5, k(1) = 7.8 X 10(5) M(-1), n(2) = 2 6.3, k(2) = 1.9 X 10(4) M(-1); indobufen, n(1) = 5.8, k(1) = 5.8 X 10( 5) M(-1), n(2) = 19.9, k(2) = 3.8 X 10(5) M(-1), where n(i) the number of binding sites of the i class and k(i) the corresponding associatio n constant.