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Titolo:
A MONOCLONAL-ANTIBODY THAT RECOGNIZES THE GPIIB IIIA ANTAGONIST DMP-728 - REVERSAL OF THE EFFECTS OF DMP-728 ON PLATELET-AGGREGATION AND BLEEDING-TIME IN THE DOG/
Autore:
REILLY TM; MOUSA SA; RACANELLI AL; THOOLEN MJ; FLINT SK; BOZARTH JM; MU DX; WALTON HL;
Indirizzi:
DUPONT MERCK PHARMACEUT CO,CARDIOVASC DIS RES,POB 80400 WILMINGTON DE19880
Titolo Testata:
Arteriosclerosis, thrombosis, and vascular biology
fascicolo: 12, volume: 15, anno: 1995,
pagine: 2195 - 2199
SICI:
1079-5642(1995)15:12<2195:AMTRTG>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOPROTEIN IIB/IIIA; DISEASE; ACTIVATION; INTEGRIN; RECEPTOR; BLOOD; DEATH; IIIA;
Keywords:
GLYCOPROTEIN IIB/IIIA; DMP 728; PLATELET ANTIBODY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
23
Recensione:
Indirizzi per estratti:
Citazione:
T.M. Reilly et al., "A MONOCLONAL-ANTIBODY THAT RECOGNIZES THE GPIIB IIIA ANTAGONIST DMP-728 - REVERSAL OF THE EFFECTS OF DMP-728 ON PLATELET-AGGREGATION AND BLEEDING-TIME IN THE DOG/", Arteriosclerosis, thrombosis, and vascular biology, 15(12), 1995, pp. 2195-2199

Abstract

Since hemorrhagic events represent a major safety concern associated with the use of new antithrombotic thera pies such as glycoprotein (GP) IIb/lIIa receptor blockade, we evaluated the ability of a monoclonalantibody recognizing DMP 728 (cyclic argininyl-gly-cyl-L-aspartyl-3-aminomethyl-benzoic acid] methanesulfonic acid salt), a potent GPIIb/IIIa receptor antagonist, to reverse the pharmacological actions of DMP 728 in the dog. DC11 was chosen for in vivo evaluation based on its ability to inhibit the binding of [H-3]DMP 728 to activated platelets and to attenuate the inhibition of ADP-induced aggregation on platelet-rich plasma ex vivo by DMP 728. After anesthesia mongrel dogs were given DMP 728 (20 mu g/kg body wt IV) infused into the femoral vein, bleeding times were determined using a Simplate device from incisions on the backside of the tongue, and platelet aggregation was determined ex vivo. Nearly complete inhibition of platelet aggregation was observed for the dogs treated with DMP 725 (20 ug/kg IV) for up to 210 minutes, and bleeding times were prolonged >15 minutes for 2 hours and remainedelevated for more than 4 hours. DC11 (0.2 or 1.0 mg/kg body wt IV) given to dogs 10 minutes after DMP 728 resulted in 50% attenuation of the effect of DMP 728 on aggregation at 3 hours. Approximately 34% inhibition of the DMP 728-mediated bleeding time was achieved at 1 hour with the 0.2 mg/kg dose, whereas approximately 50% inhibition of the bleeding time was observed for the 1 mg/kg dose at 1 hour. The bleeding time for the higher dose of DC11 returned to control levels at 2 hours, whereas the lower dose of DC11 returned to control levels al 3 hours. These results suggest that monoclonal antibody DC11 may have potentialutility as an antidote to DMP 728 in neutralizing any unexpected bleeding complications associated with its use.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/11/20 alle ore 21:38:14