DOI: 10.1161/01.cir.93.3.537. Oral Antiplatelet, Antithrombotic Efficacy of DMP 728, a Novel Platelet GPIIb/IIIa Antagonist

Oral Antiplatelet, Antithrombotic Efficacy of DMP 728, a Novel Platelet GPIIb/IIIa Antagonist

10.1161/01.cir.93.3.537

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

Background Currently used antiplatelet drugs, including aspirin and ticlopidine, are effective against certain but not all of the many endogenous platelet activators. Because of their limited efficacy, a significant number of serious thromboembolic complications still occur, highlighting the need for a more effective therapy. DMP 728 has been characterized as a potent and specific platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist. The goals of the present study were to determine the oral antiplatelet and antithrombotic efficacies of DMP 728 in various arterial thrombosis models in dogs. Methods and Results In conscious and anesthetized mongrel dogs, DMP 728 at 0.02 to 1.0 mg/kg PO in gelatin capsules produced dose-dependent antiplatelet effects in inhibiting ex vivo platelet aggregation induced by ADP and prolonging template bleeding time. DMP 728 effects on bleeding time prolongation could be reversed more rapidly than those on platelet aggregation inhibition. A maximal antiplatelet effect for DMP 728 was demonstrated at 1.0 mg/kg PO. DMP 728 demonstrated dose-dependent oral antiplatelet effects with an absolute oral bioavailability of 8% to 12% in dogs. Additionally, the antithrombotic efficacy of DMP 728 was examined after intravenous and oral administration at different doses in various models of arterial thrombosis. In the coronary artery Folts’ model in dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01 mg/kg IV and <0.6 mg/kg PO. Additionally, DMP 728 at 0.1 and 1.0 mg/kg IV or PO demonstrated 60% to 100% prevention of primary thrombosis ( P <.01) in an electrolytically induced carotid artery thrombosis model in dogs. Conclusions These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic potential as an oral antithrombotic agent in coronary and carotid artery thromboembolic disorders.

Bibliography

Mousa, S. A., DeGrado, W. F., Mu, D.-X., Kapil, R. P., Lucchesi, B. R., & Reilly, T. M. (1996). Oral Antiplatelet, Antithrombotic Efficacy of DMP 728, a Novel Platelet GPIIb/IIIa Antagonist. Circulation, 93(3), 537â543.

Authors 6

Shaker A. Mousa (first)
William F. DeGrado (additional)
Dun-Xu Mu (additional)
Ram P. Kapil (additional)
Benedict R. Lucchesi (additional)
Thomas M. Reilly (additional)

References 33 Referenced 37

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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:34 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 11:31 a.m.)
Indexed	4 weeks ago (Aug. 2, 2025, 12:50 a.m.)
Issued	29 years, 6 months ago (Feb. 1, 1996)
Published	29 years, 6 months ago (Feb. 1, 1996)
Published Print	29 years, 6 months ago (Feb. 1, 1996)

Funders 0

None

BibTeX

@article{Mousa_1996, title={Oral Antiplatelet, Antithrombotic Efficacy of DMP 728, a Novel Platelet GPIIb/IIIa Antagonist}, volume={93}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.93.3.537}, DOI={10.1161/01.cir.93.3.537}, number={3}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Mousa, Shaker A. and DeGrado, William F. and Mu, Dun-Xu and Kapil, Ram P. and Lucchesi, Benedict R. and Reilly, Thomas M.}, year={1996}, month=feb, pages={537–543} }

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