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Titolo:
ORAL ANTIPLATELET, ANTITHROMBOTIC EFFICACY OF DMP-728, A NOVEL PLATELET GPIIB IIIA ANTAGONIST/
Autore:
MOUSA SA; DEGRADO WF; MU DX; KAPIL RP; LUCCHESI BR; REILLY TM;
Indirizzi:
DUPONT MERCK PHARMACEUT CO,EXP STN,E400-3456 WILMINGTON DE 19880
Titolo Testata:
Circulation
fascicolo: 3, volume: 93, anno: 1996,
pagine: 537 - 543
SICI:
0009-7322(1996)93:3<537:OAAEOD>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOPROTEIN-IIB/IIIA; UNSTABLE ANGINA; ACTIVATION; DISEASE; INVIVO; CANINE; MODEL; IIIA; THROMBOSIS; INTEGRIN;
Keywords:
PLATELET AGGREGATION INHIBITORS; THROMBOSIS; RECEPTOR ANTAGONISTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
S.A. Mousa et al., "ORAL ANTIPLATELET, ANTITHROMBOTIC EFFICACY OF DMP-728, A NOVEL PLATELET GPIIB IIIA ANTAGONIST/", Circulation, 93(3), 1996, pp. 537-543

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 728in various arterial thrombosis models in dogs. Methods and Results Inconscious and anesthetized mongrel dogs, DMP 728 at 0.02 to 1.0 mg/kgPO 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 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 Felts' modelin dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01mg/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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 04:50:15