The Kinetics of Integrilin Limited by Obesity: A multicenter randomized pharmacokinetic and pharmacodynamic clinical trial

John P. Vavalle, Susanna R. Stevens, Nancy Hassinger, Mauricio G Cohen, Anita Arnold, David E. Kandzari, Frank V. Aguirre, Daniel D. Gretler, John H. Alexander

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Methods: Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Results: Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P <.001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P =.001). Conclusions: Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients.

Original languageEnglish
Pages (from-to)996-1002
Number of pages7
JournalAmerican Heart Journal
Volume162
Issue number6
DOIs
StatePublished - Dec 1 2011

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Pharmacokinetics
Obesity
Clinical Trials
Weights and Measures
Ideal Body Weight
Percutaneous Coronary Intervention
Body Weight
eptifibatide
Platelet Aggregation
Blood Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The Kinetics of Integrilin Limited by Obesity : A multicenter randomized pharmacokinetic and pharmacodynamic clinical trial. / Vavalle, John P.; Stevens, Susanna R.; Hassinger, Nancy; Cohen, Mauricio G; Arnold, Anita; Kandzari, David E.; Aguirre, Frank V.; Gretler, Daniel D.; Alexander, John H.

In: American Heart Journal, Vol. 162, No. 6, 01.12.2011, p. 996-1002.

Research output: Contribution to journalArticle

Vavalle, JP, Stevens, SR, Hassinger, N, Cohen, MG, Arnold, A, Kandzari, DE, Aguirre, FV, Gretler, DD & Alexander, JH 2011, 'The Kinetics of Integrilin Limited by Obesity: A multicenter randomized pharmacokinetic and pharmacodynamic clinical trial', American Heart Journal, vol. 162, no. 6, pp. 996-1002. https://doi.org/10.1016/j.ahj.2011.09.014
Vavalle, John P. ; Stevens, Susanna R. ; Hassinger, Nancy ; Cohen, Mauricio G ; Arnold, Anita ; Kandzari, David E. ; Aguirre, Frank V. ; Gretler, Daniel D. ; Alexander, John H. / The Kinetics of Integrilin Limited by Obesity : A multicenter randomized pharmacokinetic and pharmacodynamic clinical trial. In: American Heart Journal. 2011 ; Vol. 162, No. 6. pp. 996-1002.
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abstract = "Background: KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Methods: Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Results: Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P <.001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P =.001). Conclusions: Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients.",
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AU - Cohen, Mauricio G

AU - Arnold, Anita

AU - Kandzari, David E.

AU - Aguirre, Frank V.

AU - Gretler, Daniel D.

AU - Alexander, John H.

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