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Titolo:
The effect of a novel glycoprotein IIb/IIIa antagonist, SR 121566A, on platelet aggregation and activation in rhesus monkeys
Autore:
Santillan, MKO; Herring, J; Hoppensteadt, DA; Jeske, W; Herbert, JM; Fareed, J;
Indirizzi:
Loyola Univ, Med Ctr, Dept Pathol, Thrombosis & Hemostasis Labs, Maywood, IL 60153 USA Loyola Univ Maywood IL USA 60153 & Hemostasis Labs, Maywood, IL 60153 USA Sanofi Rech, F-31036 Toulouse, France Sanofi Rech Toulouse France F-31036 anofi Rech, F-31036 Toulouse, France
Titolo Testata:
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
fascicolo: 1, volume: 7, anno: 2001,
pagine: 10 - 15
SICI:
1076-0296(200101)7:1<10:TEOANG>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
IIB-IIIA ANTAGONIST; RECEPTOR ANTAGONISTS; FIBRINOGEN RECEPTOR; BINDING; POTENT; ANTIPLATELET; CLOPIDOGREL; SR121566A; ASPIRIN;
Keywords:
antiplatelet; glycoprotein IIb/IIIa; primates; pharmacokinetics; plate aggregation; flow cytometry;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Fareed, J Loyola Univ, Med Ctr, Dept Pathol, Thrombosis & Hemostasis Labs,2160 S 1st Ave, Maywood, IL 60153 USA Loyola Univ 2160 S 1st Ave Maywood IL USA 60153 od, IL 60153 USA
Citazione:
M.K.O. Santillan et al., "The effect of a novel glycoprotein IIb/IIIa antagonist, SR 121566A, on platelet aggregation and activation in rhesus monkeys", CL APPL T-H, 7(1), 2001, pp. 10-15

Abstract

SR 121566A represents a peptidomimetic glyco protein IIb/IIIa (GP IIb/IIIa) inhibitor 3-[N-{4-[4-(aminoiminomethyl)phenyl]-1,3-thiazol-2-yl}-N-(1-carboxymethylpiperid-4-yl) amino] propionic acid, trihydrochloride. To investigate the intravenous and subcutaneous pharmacodynamics of this agent, a primate model (Macaca mulatta) was used. The IC50 for adenosine diphosphate (ADP) (10 mu mol/l)-induced platelet aggregation in this primate platelet system was found to be 45 +/- 6 nmol/L. Comparatively in the human platelet rich plasma system, SR 121566A demonstrated an IC50 of 39 +/- 4 nmol/L. Graded doses of SR 121566A in the range of 25-400 mug/kg were administered intravenously. Blood samples were drawn from individual groups of primates (n = 4-6) at varying periods of time up to 24 hours after administration of SR 121566A. The pharmacodynamic effects were measured by platelet aggregation using ADP (10 mu mol/L) as an agonist. In addition, flow cytometric methods were used to measure thrombin receptor-activating peptide (TRAP) (6.25 mu mol/L)-induced platelet activation. In the subcutaneous studies, 50, 100, 250, and 400 mug/kg of SR 121566A was administered with an identical blood-drawing schedule and analysis as with the intravenous studies. In the intravenous studies, all closes of SR 121566A produced > 80% inhibition of platelet aggregation 5 minutes after the administration of the drug. The duration of the inhibitory effect is proportional to the dose administered and the 50% recovery time ranged from 2 to 15 hours. By flow cytometry, TRAP-inducedP-selectin expression was also blocked for a varying duration of time in adose-dependent fashion. The subcutaneous studies showed > 90% inhibition of platelet aggregation, which was observed at 15 minutes after administration of both 50 and 100 mug/kg of the drug. The recovery time after the subcutaneously administered doses was found to be shorter than the intravenouslyadministered doses. These studies demonstrate that SR 121566A is an effective platelet inhibitor with predictable pharmacokinetic and pharmacodynamiccharacteristics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 12:42:25