Reversible and Non-Competitive Inhibition of Cyclooxygenase by Indobufen for Efficient Antiplatelet Action and Relief of Gastrointestinal Irritation.

Abstract

Clinically, indobufen is widely used for the treatment of antiplatelet aggregation and anticoagulation. Prior studies have discovered that abnormal platelet function can be promptly restored to normal when the drug is stopped. Herein, through the study of the enzyme reaction kinetics, we demonstrated that the inhibitory effect of indobufen on cyclooxygenase-1 (COX-1) was reversible and non-competitive. Specifically, the cyclooxygenase inhibition experiment showed that the level of 6-keto-PGF1α in the gastric mucosa of the indobufen-treated groups was significantly higher than that of the aspirin group (###p < 0.001), indicating a higher level of PGI2 in and a better physiological state of the gastric mucosa. Moreover, the rat gastric ulcer index and mucosal section experiments further confirmed the relief of gastrointestinal irritation and the adverse reaction rate of the indobufen-treated group compared to those of the aspirin group. Furthermore, indobufen was verified to exert reversible inhibitory activity on the heme group of COX-1 and thus reversibly inhibit COX-1 activity. In general, compared with aspirin, the long-term oral administration of indobufen yields a lower risk of gastrointestinal symptoms, such as ulcers.