Liu Jia, Sun Peng, Qi Xiaole
School of International Pharmaceutical Business, China Pharmaceutical University, #639 Longmian Dadao, Jiangning District, Nanjing 211189, China.
School of Pharmacy, China Pharmaceutical University, #639 Longmian Dadao, Jiangning District, Nanjing 210009, China.
Pharmaceutics. 2023 Aug 14;15(8):2135. doi: 10.3390/pharmaceutics15082135.
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 ( < 0.001), indicating a higher level of PGI 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.
临床上，吲哚布芬被广泛用于抗血小板聚集和抗凝治疗。先前的研究发现，停药后血小板功能异常可迅速恢复正常。在此，通过酶反应动力学研究，我们证明吲哚布芬对环氧合酶-1（COX-1）的抑制作用是可逆的且非竞争性的。具体而言，环氧合酶抑制实验表明，吲哚布芬治疗组胃黏膜中6-酮-前列环素F1α水平显著高于阿司匹林组（<0.001），表明胃黏膜中前列环素水平更高，生理状态更好。此外，大鼠胃溃疡指数和黏膜切片实验进一步证实，与阿司匹林组相比，吲哚布芬治疗组的胃肠道刺激缓解，不良反应率降低。此外，已证实吲哚布芬对COX-1的血红素基团具有可逆抑制活性，从而可逆地抑制COX-1活性。总体而言，与阿司匹林相比，长期口服吲哚布芬产生胃肠道症状（如溃疡）的风险较低。
