Phase I study of eptifibatide in patients with sickle cell anaemia.
The alphaIIbbeta3 antagonist eptifibatide is an effective treatment for patients with acute coronary syndromes (ACS). Platelet reactivity and CD40 ligand (CD40L) may play a role in the pathophysiology of sickle cell anaemia (SCA) similar to that in ACS, suggesting that inhibition of platelet aggregation and CD40L release by eptifibatide may benefit patients with SCA. Following eptifibatide infusion, safety and pharmacodynamic data were obtained from four SCA patients in their non-crisis, steady states. Eptifibatide was well tolerated, with no adverse changes in the haematological, biochemical or coagulation parameters studied. Eptifibatide did not increase plasma levels of platelet factor 4 or beta-thromboglobulin, P-selectin exposure or platelet:leucocyte aggregate formation. Moreover, decreases in platelet aggregation and soluble CD40L (sCD40L) levels achieved in SCA patients were comparable to those observed in the treatment of ACS. Finally, indicators of inflammation, macrophage inflammatory protein-1alpha, tumour necrosis factor-alpha and myoglobin were reduced following eptifibatide infusion, while vasodilation correlatives, matrix metalloproteinases (MMP-2 and MMP-9) and leptin were increased. Based on these phase I results, eptifibatide may benefit SCA patients by inhibiting platelet aggregation, decreasing sCD40L levels and favourably altering plasma levels of inflammatory mediators.
Lee
Sheritha P
SP
Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.
Ataga
Kenneth I
KI
Zayed
Mohamed
M
Manganello
Jeanne M
JM
Orringer
Eugene P
EP
Phillips
David R
DR
Parise
Leslie V
LV
D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000077542:Eptifibatide; D055436:Growth Differentiation Factor 15; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
D019013:CD40 Antigens; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D020782:Matrix Metalloproteinases; D000077542:Eptifibatide