Je. Tcheng et al., Clinical pharmacology of higher dose eptifibatide in percutaneous coronaryintervention (the PRIDE study), AM J CARD, 88(10), 2001, pp. 1097-1102
Citations number
24
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
This study describes the dose-exploration phase of the PRIDE trial, an inve
stigation of the clinical pharmacology of higher dose eptifibatide in patie
nts who underwent elective percutaneous coronary intervention (PCI). Outcom
es of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dep
endent upon proper dosing selection. In this multicenter, placebo-controlle
d clinical study, 127 patients were randomized 1:1:2:2 into 1 of the follow
ing treatment groups: placebo; eptifibatide as a 135 mug/kg bolus followed
by a 0.75 mug/kg/min infusion; eptifibatide as a 180 mug/kg bolus with a 2.
0 mug/kg/min infusion; or eptifibatide as a 250 mug/kg bolus with a 3.0 mug
/kg/min infusion. Light transmission aggregometry was used to determine pla
telet aggregation in response to 20 muM adenosine diphosphate, and platelet
receptor occupancy was also determined. Eptifibatide exhibited linear phar
macokinetics over the dose range studied. Inhibition of platelet aggregatio
n was greater in samples collected in sodium citrate compared with those co
llected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/
2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediat
ely (5 minutes) and at steady state (8 to 24 hours). At 1hour, mean inhibit
ion of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent
pharmacodynamics that were dependent upon choice of anticoagulant. A 180 mu
g/kg bolus followed by a 2.0 mug/kg/min infusion at steady state achieved >
80% inhibition of platelet aggregation. With the single-bolus regimen, howe
ver, there was an early loss of the inhibition of platelet aggregation befo
re steady state was reached. Additional dose-exploration studies may furthe
r optimize eptifibatide dosing. (C) by Excerpta Medica, Inc.