title: Dosing strategy in patients with renal failure receiving enoxaparin for the treatment of non-ST-segment elevation acute coronary syndrome.
abstract: BACKGROUND
  Enoxaparin therapy is recommended for the initial treatment of patients with non-ST-segment elevation acute coronary syndrome. However, little dosing information is available regarding the use of enoxaparin in patients with renal impairment.
  
  
  METHODS
  We conducted a population pharmacokinetic analysis using anti-Xa activities measured in 532 patients (normal renal function in 34%, mild renal impairment in 36%, moderate renal impairment in 20%, and severe renal impairment in 10%) receiving subcutaneous enoxaparin (mean weight-corrected dose [+/-SD], 0.83 +/- 0.19 mg x kg(-1) x 12 h(-1) for an acute coronary syndrome. Simulations were then performed to develop a dosing strategy for patients with renal impairment.
  
  
  RESULTS
  A 1-compartment model with first-order kinetics best fit the data. The covariate analysis showed that enoxaparin clearance was related to renal function and volume of distribution to total body weight. Enoxaparin clearance was decreased by 31% in patients with moderate renal impairment and by 44% in patients with severe renal impairment, resulting in a significant accumulation with the use of the standard 1 mg . kg(-1) x 12 h(-1) dosing regimen. Simulations showed that a first unadjusted dose of 1 mg/kg followed by a regimen of 0.8 mg . kg(-1) x 12 h(-1) in patients with moderate renal impairment or 0.66 mg . kg(-1) x 12 h(-)1 in patients with severe renal impairment should avoid accumulation of enoxaparin and keep peak anti-Xa activities between 0.5 and 1.2 IU/mL for a large majority of patients.
  
  
  CONCLUSIONS
  An enoxaparin dosage reduction should be considered in acute coronary syndrome patients with creatinine clearance lower than 50 mL/min. A simple dosing protocol for enoxaparin to avoid significant accumulation in patients with moderate or severe renal impairment is proposed.
authors.affiliation: Pharmacology Department, Institute of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France. jean-sebastien.hulot@psl.aphp.fr
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Philippe
authors.initials: P
authors.lastname: Lechat
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Annick
authors.initials: A
authors.lastname: Ankri
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D015951:Factor Xa