Antiplatelet and Antithrombotic Effects of a Combination of Ticlopidine and Ginkgo biloba Ext (EGb 761)

Kim, Yeong Shik; Pyo, Mi Kyung; Park, Kyung Mi; Park, Pyung Hee; Hahn, Bum-Soo; Wu, Song; Yun‐Choi, Hye Sook

doi:10.1016/s0049-3848(98)00075-9

Cited by 57 publications

(25 citation statements)

References 14 publications

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“…The causes of the separation of antithrombotic and bleeding time effects of BM-573 remain unknown. In contrast, ticlopidine, an ADP receptor antagonist, significantly increased bleeding time tendency, as observed by different authors (Kim et al, 1998;Foster et al, 2001). Finally, we examined both the diuretic and hypoglycemic properties of BM-573 compared with torasemide and glibenclamide, respectively.…”

Section: Discussionsupporting

confidence: 54%

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Dogné¹,

Hanson²,

Leval³

et al. 2004

J Pharmacol Exp Ther

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The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-NЈ-[2-(4Ј-methylphenylamino)-5-nitrobenzenesulfonyl]urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F 2 )-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50 Ϯ 5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16 Ϯ 0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia.The isozymes cyclooxygenase (COX)-1 and -2 catalyze the conversion of arachidonic acid into thromboxane A 2 (TXA 2 ) and prostaglandins (PGs). The eicosanoid TXA 2 is the major COX-1 product of arachidonic acid metabolism in platelets.

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Section: Discussionsupporting

confidence: 54%

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Dogné¹,

Hanson²,

Leval³

et al. 2004

J Pharmacol Exp Ther

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“…Many studies have demonstrated that the combination treatment of aniplatelet agents could be beneficial in cerebral and peripheral arterial disease (Kim et al, 1998;Aldandashi et al, 2007;Fontana and Reny, 2007). Moreover, G. biloba extract enhanced the antiplatelet and antithrombotic effects of cilostazol without the prolongation of bleeding time (our unpublished data).…”

Section: Introductionmentioning

confidence: 57%

“…Recently, several reports have been published that combination therapies of antiplatelet agents were more effective than a single drug administration (Kim et al, 1998;Aldandashi et al, 2007;Fontana and Reny, 2007). However, for such a combination therapy, drug interactions should be considered to prevent likely side-effects caused by concomitant use of these agents.…”

Section: Discussionmentioning

confidence: 99%

Negligible Effect of Ginkgo Biloba Extract on the Pharmacokinetics of Cilostazol

Chung¹,

Kim²,

Kim³

et al. 2009

Biomolecules and Therapeutics

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-Ginkgo biloba (G. biloba) extract is a widely used phytomedicine for the oral treatment of peripheral vascular disease. Cilostazol is a synthetic antiplatelet and vasodilating agent for the treatment of intermittent claudication resulting from peripheral arterial disease. It is likely to use concomitantly G. biloba extract and cilostazol for the treatment of peripheral arterial disease, which raises a concern of increasing their adverse effects of herbal-drug interactions. To clarify any possible herbal-drug interaction between G. biloba extract and cilostazol, the effect of the G. biloba extract on the pharmacokinetics of cilostazol was investigated. As cilostazol is known to be eliminated mainly by cytochrome P450 (CYP)-mediated metabolism, we investigated the effects of G. biloba extract on the human CYP enzyme activities and the effect of G. biloba extract on the pharmacokinetics of cilostazol after co-administration of the two agents to male beagle dogs. The G. biloba extract inhibited more or less CYP2C8, CYP2C9, and CYP2C19 enzyme activities in the in vitro microsomal study with IC50 values of 30.8, 60.5, and 25.2 μg/ml, respectively. In the pharmacokinetic study, co-administration with the G. biloba extract had no significant effect on the pharmacokinetics of cilostazol in dogs, although CYP2C has been reported to be responsible for the metabolism of cilostazol. In conclusion, these results suggest that there may not be a pharmacokinetic interaction between G. biloba extract and cilostazol.

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“…85,86 Therefore, there is concern regarding increased risk of bleeding with ginkgo when coadministered with anticoagulants (Table 2) or antiplatelet drugs such as ticlopidine. 87 Bleeding events attributed to ginkgo use in warfarin-associated intracerebral hemorrhage, 88 ibuprofen-associated intracerebral mass bleeding, 89 aspirin-associated spontaneous hyphema, 90 postoperative bleeding 91 and subphrenic hematoma requiring laparoscopic evacuation 92 have been reported.…”

Section: Ginkgomentioning

confidence: 99%

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

Sultan¹,

Maria²,

Ali³

et al. 2015

Journal of Patient-Centered Research and Reviews

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Antiplatelet and Antithrombotic Effects of a Combination of Ticlopidine and Ginkgo biloba Ext (EGb 761)

Cited by 57 publications

References 14 publications

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Negligible Effect of Ginkgo Biloba Extract on the Pharmacokinetics of Cilostazol

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

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Antiplatelet and Antithrombotic Effects of a Combination of Ticlopidine and Ginkgo biloba Ext (EGb 761)

Cited by 57 publications

References 14 publications

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A2 Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A2 Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Negligible Effect of Ginkgo Biloba Extract on the Pharmacokinetics of Cilostazol

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

Contact Info

Product

Resources

About

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time

Pharmacological Characterization of N-tert-Butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A₂ Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time