RT Journal Article
SR Electronic
T1 Glycoprotein IIb/IIIa Receptor Antagonist  (2<em>S</em>)-2-[(2-Naphthyl-sulfonyl)amino]-3-{[2-({4-(4-piperidinyl)-2-[2-(4-piperidinyl)ethyl]  butanoyl}amino)acetyl]amino}propanoic Acid Dihydrochloride (CRL42796), in  Combination with Aspirin and/or Enoxaparin, Prevents Coronary Artery  Rethrombosis after Successful Thrombolytic Treatment by Recombinant Tissue  Plasminogen Activator
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 616
OP 623
DO 10.1124/jpet.103.052886
VO 306
IS 2
A1 Ting-Ting Hong
A1 Edward M. Driscoll
A1 Andrew J. White
A1 Ardaman Sherigill
A1 Thierry A. Giboulot
A1 Benedict R. Lucchesi
YR 2003
UL http://jpet.aspetjournals.org/content/306/2/616.abstract
AB The antithrombotic effect of the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist (2S)-2-[(2-naphthyl-sulfonyl)amino]-3-{[2-({4-(4-piperidinyl)-2-[2-(4-piperidinyl)ethyl] butanoyl}amino)acetyl]amino} propanoic acid dihydrochloride (CRL42796), administered alone, or in combination with aspirin, and/or enoxaparin, was examined in a canine left circumflex (LCX) coronary artery rethrombosis model. The electrolytic induction of arterial thrombosis was followed by intracoronary recombinant tissue plasminogen activator administration to achieve thrombolysis, and the adjunctive therapy was initiated 15 min earlier and maintained for 4 h. Thirty-five purpose-bred beagle dogs were randomized to receive one of the following treatments: group 0 (n = 6, placebo); group 1 (n = 6, CRL42796 15 μg/kg i.v. loading dose followed by 0.31 μg/kg/min i.v. infusion), group 2 (n = 6, aspirin 7 mg/kg, administered orally, at –47, –23, –17 h before entry into the experimental protocol); group 3 (n = 6, aspirin + CRL42796); group 4 (n = 6, aspirin + enoxaparin 0.6 μg/kg i.v. loading dose followed by 6.0 μg/kg/min i.v. infusion); and group 5 (n = 5, aspirin + CRL42796 + enoxaparin). The incidence of LCX reocclusion was as follows: group 0, 6/6; group 1, 3/6; group 2, 5/6; group 3, 2/6; group 4, 2/6; and group 5, 0/5. Aspirin pretreatment increased the tongue-bleeding time, whereas the addition of CRL42796 or enoxaparin did not prolong bleeding time to a further degree. However, the combination of the three drugs did increase bleeding time significantly, from 173.9 ± 19.8 to 620.0 ± 98.7 s. In conclusion, low-dose CRL42796 together with aspirin and enoxaparin prevented coronary artery rethrombosis, although bleeding time was prolonged. The latter may be of concern in the clinical use of combination therapy. The American Society for Pharmacology and Experimental Therapeutics