Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (The PRIDE Study)

James E. Tcheng, J. David Talley, J. Conor O'Shea, Ian C. Gilchrist, Neal S. Kleiman, Cindy L. Grines, Charles J. Davidson, A. Michael Lincoff, Robert M. Califf, Lisa K. Jennings, Michael M. Kitt, Todd J. Lorenz

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Abstract

This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 μg/kg bolus followed by a 0.75 μg/kg/min infusion; eptifibatide as a 180 μg/kg bolus with a 2.0 μg/kg/min infusion; or eptifibatide as a 250 μg/kg bolus with a 3.0 μg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 μM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 μg/kg bolus followed by a 2.0 μg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.

Original languageEnglish (US)
Pages (from-to)1097-1102
Number of pages6
JournalAmerican Journal of Cardiology
Volume88
Issue number10
DOIs
StatePublished - Nov 15 2001

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Clinical Pharmacology
Percutaneous Coronary Intervention
Platelet Aggregation
Placebos
Integrin beta3
Platelet Glycoprotein GPIIb-IIIa Complex
eptifibatide
Adenosine Diphosphate
Anticoagulants
Arginine
Blood Platelets
Pharmacokinetics
Light

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Tcheng, James E. ; Talley, J. David ; O'Shea, J. Conor ; Gilchrist, Ian C. ; Kleiman, Neal S. ; Grines, Cindy L. ; Davidson, Charles J. ; Lincoff, A. Michael ; Califf, Robert M. ; Jennings, Lisa K. ; Kitt, Michael M. ; Lorenz, Todd J. / Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (The PRIDE Study). In: American Journal of Cardiology. 2001 ; Vol. 88, No. 10. pp. 1097-1102.
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abstract = "This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 μg/kg bolus followed by a 0.75 μg/kg/min infusion; eptifibatide as a 180 μg/kg bolus with a 2.0 μg/kg/min infusion; or eptifibatide as a 250 μg/kg bolus with a 3.0 μg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 μM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90{\%} inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80{\%}. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 μg/kg bolus followed by a 2.0 μg/kg/min infusion at steady state achieved >80{\%} inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.",
author = "Tcheng, {James E.} and Talley, {J. David} and O'Shea, {J. Conor} and Gilchrist, {Ian C.} and Kleiman, {Neal S.} and Grines, {Cindy L.} and Davidson, {Charles J.} and Lincoff, {A. Michael} and Califf, {Robert M.} and Jennings, {Lisa K.} and Kitt, {Michael M.} and Lorenz, {Todd J.}",
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Tcheng, JE, Talley, JD, O'Shea, JC, Gilchrist, IC, Kleiman, NS, Grines, CL, Davidson, CJ, Lincoff, AM, Califf, RM, Jennings, LK, Kitt, MM & Lorenz, TJ 2001, 'Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (The PRIDE Study)', American Journal of Cardiology, vol. 88, no. 10, pp. 1097-1102. https://doi.org/10.1016/S0002-9149(01)02041-0

Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (The PRIDE Study). / Tcheng, James E.; Talley, J. David; O'Shea, J. Conor; Gilchrist, Ian C.; Kleiman, Neal S.; Grines, Cindy L.; Davidson, Charles J.; Lincoff, A. Michael; Califf, Robert M.; Jennings, Lisa K.; Kitt, Michael M.; Lorenz, Todd J.

In: American Journal of Cardiology, Vol. 88, No. 10, 15.11.2001, p. 1097-1102.

Research output: Contribution to journalArticle

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AU - Tcheng, James E.

AU - Talley, J. David

AU - O'Shea, J. Conor

AU - Gilchrist, Ian C.

AU - Kleiman, Neal S.

AU - Grines, Cindy L.

AU - Davidson, Charles J.

AU - Lincoff, A. Michael

AU - Califf, Robert M.

AU - Jennings, Lisa K.

AU - Kitt, Michael M.

AU - Lorenz, Todd J.

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N2 - This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 μg/kg bolus followed by a 0.75 μg/kg/min infusion; eptifibatide as a 180 μg/kg bolus with a 2.0 μg/kg/min infusion; or eptifibatide as a 250 μg/kg bolus with a 3.0 μg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 μM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 μg/kg bolus followed by a 2.0 μg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.

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