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Comparative Study
. 2018 Jun 15;23(6):1452.
doi: 10.3390/molecules23061452.

Anticoagulant Activities of Indobufen, an Antiplatelet Drug

Jia Liu  1 , Dan Xu  2 , Nian Xia  3 , Kai Hou  4 , Shijie Chen  5 , Yu Wang  6 , Yunman Li  7
Affiliations
Comparative Study

Anticoagulant Activities of Indobufen, an Antiplatelet Drug

Jia Liu et al. Molecules. .

Abstract

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.

Keywords: anticoagulant effect; coagulation factor; indobufen; platelet factor..

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical structure of indobufen.
Figure 2
Figure 2
The effects of indobufen on activated partial thromboplastin time (APTT, A), prothrombin time PT, B), and thrombin time (TT, C) in rabbits. ** p < 0.01 versus the control group ## p < 0.01 versus the warfarin sodium group (mean ± S.D., n = 9).
Figure 3
Figure 3
The effects of indobufen on bleeding time (A) and clotting time (B) in mice. * p < 0.05, ** p < 0.01 versus the control group; (mean ± S.D., n = 10).
Figure 4
Figure 4
The effects of indobufen on coagulation factor 1 (FI, A), 2 (FII, B), 5 (FV, C),8 (FVIII, D), 10 (FX, E), and platelet factor 3 (PF3, F), 4 (PF4, G) in the poor platelet plasma (PPP) of rabbits. * p < 0.05, ** p < 0.01 versus the control group; ## p < 0.01 versus warfarin sodium group (mean ± S.D., n = 9).
Figure 5
Figure 5
The effects of indobufen on thrombosis formation in a rat model of an arteriovenous shunt. (A) The results of wet thrombus inhibition. (B) The results of dry thrombus inhibition. * p < 0.05, ** p < 0.01 versus the rivaroxaban 1 mg/kg group (mean ± S.D., n = 8).
Figure 6
Figure 6
The effects of indobufen on the content of coagulation factor 2 (FII) in rats. ** p < 0.01 versus the control group; # p < 0.05, versus the dabigatran 30 mg/kg group (mean ± S.D., n = 10).
Figure 7
Figure 7
The effects of indobufen on the content of coagulation factor 10 (FX) in rats. * p < 0.05, ** p < 0.01 versus the control group; △ p < 0.05 versus the rivaroxaban 1 mg/kg group (mean ± S.D., n = 10).
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