Anticoagulant Activities of Indobufen, an Antiplatelet Drug

Springer Science and Business Media LLC - Tập 23 Số 6 - Trang 1452
Jia Liu1, Dan Xu2, Nian Xia2, Kai Hou2, Shijie Chen2, Yu Wang3, Yunman Li2
1Department of Marketing, Hangzhou Zhongmei Huadong Pharmaceutical Company, Hangzhou 310011, China
2State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China
3Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China

Tóm tắt

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in rabbit plasma. We evaluated the anticoagulant mechanisms on the content of the platelet factor 3,4 (PF3,4), and the coagulation factor 1, 2, 5, 8, 10 (FI, II, V, VIII, X) in rabbits, as well as the in vivo bleeding time and clotting time in mice. The pharmacodynamic differences between indobufen and warfarin sodium, rivaroxaban, and dabigatran were further studied on thrombus formation and the content of FII and FX in rats. Animal experiments showed that intragastric-administrated indobufen can significantly reduce the APTT, PT, TT, PF3, FI, II, V, VIII, and X plasma contents. Its inhibitory effect on plasma FII was better than thrombin inhibitor dabigatran with effect on FX better than FXa inhibitor rivaroxaban. These results suggest that indobufen has some anticoagulant effects as strong as some conventional anticoagulants. The mechanism may be related to both exogenous and endogenous coagulation system.

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Tài liệu tham khảo

Jin, 2016, Potential blood clotting factors and anticoagulants, Biomed. Pharmacother., 84, 356, 10.1016/j.biopha.2016.09.057

Ryu, 2013, Anticoagulant and antiplatelet activities of artemisia princeps pampanini and its bioactive components, Prev. Nutr. Food Sci., 18, 181, 10.3746/pnf.2013.18.3.181

Butenas, 2002, Blood coagulation, Biochemistry, 67, 3

Prevention, 2000, The italian guidelines for stroke prevention, Neurol. Sci., 21, 5, 10.1007/s100720070112

Schuijt, 2013, Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: Lessons from a tick salivary protein, Circulation, 128, 254, 10.1161/CIRCULATIONAHA.113.003191

Qiu, 2017, Capture of anti-coagulant active ingredients from Moutan Cortex by platelet immobilized chromatography and evaluation of anticoagulant activity in rats, Biomed. Pharmacother., 95, 235, 10.1016/j.biopha.2017.08.051

Vinazzer, 1980, Clinical pharmacology studies with indobufen (K 3920): Inhibitor of platelet aggregation, J. Clin. Pharmacol., 20, 316, 10.1177/009127008002000502

Wiseman, 1992, Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cerebral, peripheral and coronary vascular disease, Drugs, 44, 445, 10.2165/00003495-199244030-00009

Posma, 2016, Coagulation and non-coagulation effects of thrombin, J. Thromb. Haemost., 14, 1908, 10.1111/jth.13441

Coleman, 2012, Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation, Int. J. Clin. Pract., 66, 53, 10.1111/j.1742-1241.2011.02809.x

Eligini, 2006, Indobufen inhibits tissue factor in human monocytes through a thromboxane-mediated mechanism, Cardiovasc. Res., 69, 218, 10.1016/j.cardiores.2005.07.013

Morocutti, 1997, Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators, Stroke, 28, 1015, 10.1161/01.STR.28.5.1015

Patrono, 2008, Antiplatelet drugs: American college of chest physicians evidence-based clinical practice guidelines (8th edition), Chest, 133, 199S, 10.1378/chest.08-0672

Mannucci, 1987, Indobufen is a potent inhibitor of whole blood aggregation in patients with a high atherosclerotic risk, Thromb. Res., 48, 417, 10.1016/0049-3848(87)90399-9

Grasselli, 1987, In vitro and ex vivo effects of indobufen on red blood cell deformability, Eur. J. Clin. Pharmacol., 32, 207, 10.1007/BF00542198

Naithani, 2008, Bilateral vitreous hemorrhage in a child due to isolated platelet factor 3 availability defect, J. AAPOS, 12, 203, 10.1016/j.jaapos.2007.09.013

Kowalska, 2010, Role of the platelet chemokine platelet factor 4 (PF4) in hemostasis and thrombosis, Thromb. Res., 125, 292, 10.1016/j.thromres.2009.11.023

Lord, 2017, Platelet factor 4 binds to vascular proteoglycans and controls both growth factor activities and platelet activation, J. Biol. Chem., 292, 4054, 10.1074/jbc.M116.760660

Heemskerk, 2013, Platelet-based coagulation: different populations, different functions, J. Thromb. Haemost., 11, 2, 10.1111/jth.12045

Samama, 2011, The mechanism of action of rivaroxaban—An oral, direct Factor Xa inhibitor—Compared with other anticoagulants, Thromb. Res., 127, 497, 10.1016/j.thromres.2010.09.008

Vinholt, 2017, Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner, J. Thromb. Thrombolysis., 44, 216, 10.1007/s11239-017-1512-2

Xu, 2017, Bleeding effected by direct oral anticoagulants study, g., direct oral anticoagulant- or warfarin-related major bleeding: Characteristics, reversal strategies, and outcomes from a multicenter observational study, Chest, 152, 81, 10.1016/j.chest.2017.02.009

Stratton, 1997, Chronic atrial fibrillation: Selection of antithrombotic therapy, Card. Electrophysiol. Rev., 1, 35, 10.1023/A:1009903216196

Carrieri, 1987, Antithrombotic effect of indobufen in an experimental model of arterio-arterial microanastomosis in the rat, Thromb. Res., 45, 195, 10.1016/0049-3848(87)90187-3

Lee, 2016, Comparison of aspirin and indobufen in healthy volunteers, Platelets, 27, 105

Group, 2001, Long term anticoagulation or antiplatelet treatment, BMJ, 323, 235

Smith, 2015, How it all starts: Initiation of the clotting cascade, Crit. Rev. Biochem. Mol. Biol., 50, 326, 10.3109/10409238.2015.1050550

Lee, 2015, Antiplatelet, anticoagulant, and profibrinolytic activities of baicalin, Arch. Pharm. Res., 38, 893, 10.1007/s12272-014-0410-9

Triplett, 2000, Coagulation and bleeding disorders: review and update, Clin. Chem., 46, 1260, 10.1093/clinchem/46.8.1260

Di, 2017, Old and new oral anticoagulants: Food, herbal medicines and drug interactions, Blood Rev., 31, 193, 10.1016/j.blre.2017.02.001

Molina, 2014, A quantitative and humane tail bleeding assay for efficacy evaluation of antihaemophilic factors in haemophilia A mice, Haemophilia, 20, e392, 10.1111/hae.12484

Kaku, 2013, Antithrombotic and anticoagulant effects of direct factor Xa inhibitor darexaban in rat and rabbit models of venous thrombosis, Eur. J. Pharmacol., 699, 40, 10.1016/j.ejphar.2012.11.026

Greene, 2010, Animal models subcommittee of the, s.; standardization committee of the, i., towards a standardization of the murine tail bleeding model, J. Thromb. Haemost., 8, 2820, 10.1111/j.1538-7836.2010.04084.x

Umar, 2015, Effect of traditional Uyghur medicine abnormal Savda Munziq extract on rabbit platelet aggregation in vitro and rat arteriovenous shunt thrombosis in vivo, J. Ethnopharmacol., 159, 184, 10.1016/j.jep.2014.11.006

ElGendy, 2014, Effects of warfarin and l-carnitine on hemostatic function and oxidative stress in streptozotocin-induced diabetic rats, J. Physiol. Biochem., 70, 535, 10.1007/s13105-014-0333-4