The kinetics of integrilin limited by obesity: a multicenter randomized pharmacokinetic and pharmacodynamic clinical trial

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.

Figure 1

Plasma concentrations of eptifibatide in the 3 dosing regimens across the spectrum of weights. Black dots and solid black line correspond to standard dosing; open circles and dashed line correspond to weight-based dosing; gray dots and solid gray line correspond to ideal body weight-based dosing. Standard dosing: slope= −6.4, Weight-based dosing: slope=20.6, Ideal weight-based dosing: slope=6.9. One patient with weight 247 kg and eptifibatide concentration 1350 ng/mL is not shown but is included in all calculations.

Figure 2

Pre- and post-eptifibatide platelet aggregation units in for each patient in the standard dosing group (a), ABW dosing group (b), and IBW dosing group (c).

Figure 2

Pre- and post-eptifibatide platelet aggregation units in for each patient in the standard dosing group (a), ABW dosing group (b), and IBW dosing group (c).

Figure 2

Pre- and post-eptifibatide platelet aggregation units in for each patient in the standard dosing group (a), ABW dosing group (b), and IBW dosing group (c).