title: 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.
authors.affiliation: Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Vavalle
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.forename: Nancy
authors.initials: N
authors.lastname: Hassinger
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Cohen
authors.forename: Anita
authors.initials: A
authors.lastname: Arnold
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.forename: Frank V
authors.initials: FV
authors.lastname: Aguirre
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gretler
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D003327:Coronary Disease / Q000150:complications / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010455:Peptides / Q000097:blood / Q000493:pharmacokinetics*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D015607:Stents
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D000077542:Eptifibatide