THE IN VITRO EFFECT OF EPTIFIBATIDE, A GLYCOPROTEIN IIb/IIIa ANTAGONIST, ON VARIOUS RESPONSES OF PORCINE BLOOD PLATELETS

被引:0
作者
Ciborowski, Michal [1 ]
Tomasiak, Marian [1 ]
机构
[1] Med Univ Bialystok, Dept Phys Chem, PL-15089 Bialystok, Poland
来源
ACTA POLONIAE PHARMACEUTICA | 2009年 / 66卷 / 03期
关键词
integrilin; aggregation; secretion; porcine platelets; GPIIb/IIIa receptors; PERCUTANEOUS CORONARY INTERVENTION; IIB-IIIA; THROMBIN GENERATION; TIROFIBAN; ABCIXIMAB; MEMBRANE; PHARMACOKINETICS; PHARMACODYNAMICS; AGGREGATION; INHIBITION;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The current study systematically evaluates the in vitro effect of eptifibatide, a GPIIb/IIIa blocker, on various responses of poreine platelets evoked by principal physiological stimulators. Eptifibatide at concentrations up to 40 mg/mL did not affect the calcium signal produced by thrombin, partly reduced the procoagulant response evoked by collagen, and strongly inhibited (IC50 similar to 11 mg/mL) adhesion of these cells to fibrinogen coated surfaces. Eptifibatide in a concentration-dependent manner reduced ADP, collagen, and thrombin-induced platelet aggregation (IC50 = 16-27 mg/mL), dense granule secretion (IC50 - 22-31 mg/mL) and lysosome secretion (IC50 = 25-50 mg/mL). Substantial (up to 30-40%) collagen or thrombin evoked platelet aggregation still occurred at high (52 mg/mL) eptifibatide concentrations. Direct comparison of the susceptibility of platelet aggregation and dense granule secretion to the inhibitory action of eptifibatide indicates that aggregation is appreciably more sensitive than secretion. Eptifibatide (8 mg/mL) added together with a low (70 mg/mL) concentration of bivalirudin (A direct thrombin inhibitor) effectively (similar to 90%) reduced platelet aggregation induced by thrombin (0.2 U/mL). Based on these results, eptifibatide is not expected to reduce efficiently thrombus formation initiated by rapid local production of large amounts of thrombin. One practical consequence of our in vitro studies is the suggestion that the anti-thrombotic efficacy of eptifibatide, especially in preventing acute thrombotic events, may be largely improved by its combination with direct thrombin inhibitors.
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页码:235 / 242
页数:8
相关论文
共 48 条
[1]  
BADIMON L, 1993, THROMB HAEMOSTASIS, V70, P111
[2]   A COLORIMETRIC METHOD FOR THE MEASUREMENT OF PLATELET-ADHESION IN MICROTITER PLATES [J].
BELLAVITE, P ;
ANDRIOLI, G ;
GUZZO, P ;
ARIGLIANO, P ;
CHIRUMBOLO, S ;
MANZATO, F ;
SANTONASTASO, C .
ANALYTICAL BIOCHEMISTRY, 1994, 216 (02) :444-450
[3]  
Bennett JS, 2001, ANN NY ACAD SCI, V936, P340
[4]   Thrombotic and infectious complications of central venous catheters in patients with hematological malignancies [J].
Boersma, R. S. ;
Jie, K. -S. G. ;
Verbon, A. ;
van Pampus, E. C. M. ;
Schouten, H. C. .
ANNALS OF ONCOLOGY, 2008, 19 (03) :433-442
[5]  
BORN GVR, 1963, J PHYSIOL-LONDON, V168, P178, DOI 10.1113/jphysiol.1963.sp007185
[6]   Networking in the hemostatic system - Integrin alpha(IIIb)beta(3) binds prothrombin and influences its activation [J].
Byzova, TV ;
Plow, EF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (43) :27183-27188
[7]  
COLLER BS, 1992, HEART CARDIOVASCULAR, P219
[8]  
*COMPARE INV, 2002, CIRCULATION, V106, P1470
[9]  
Cook JJ, 1999, CARDIOVASC DRUG REV, V17, P199
[10]   PLATELET GLYCOPROTEIN-IIB-IIIA PROTEIN ANTAGONISTS FROM SNAKE-VENOMS - EVIDENCE FOR A FAMILY OF PLATELET-AGGREGATION INHIBITORS [J].
DENNIS, MS ;
HENZEL, WJ ;
PITTI, RM ;
LIPARI, MT ;
NAPIER, MA ;
DEISHER, TA ;
BUNTING, S ;
LAZARUS, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (07) :2471-2475