A kinetic study of protein binding to ecabet sodium using quartz-crystal microbalance

To define the mechanism of the protection by ecabet sodium of the gastric m ucosa, the characteristics of protein binding of this drug were investigate d using a quartz-crystal microbalance (QCM) method. The binding rate consta nts (k(b)) and the binding amounts (Delta m) were obtained from time course s of the frequency decrease (mass increase) of the QCM, The binding constan ts to proteins of two ecabet analogues (G1, ecabet type and G2, non-ionic e cabet type) were dependent on the pH, leading to large k(b) values at the a cidic region. Furthermore, the k(b) values of G1 with the addition of bovin e serum albumin (BSA) and bovine serum fibrinogen (BSF) at the acid region were larger than those of G2, The difference in k(b) values between G1 and G2 for porcine gastric mucin (PGM) is hardly discernible. Ecabet seems to b e more heavily distributed in the ulcerous areas than in the intact mucosa, judging from the large binding constants of this drug to BSA and BSF compa red with those to PGM, It is suggested that ecabet is bound to proteins by hydrophobic interaction, moreover, the electrostatic interaction between th is drug and proteins (BSA and BSF) occurs at acidic pH region. On account o f these interactions, ecabet sodium seems to have a more protective effect on an ulcer at intraluminal acidity than sucralfate, Finally, QCM was found to be a useful technique for detecting quantitatively the time course of b inding proteins with drug.