title: Effect of renal function on the pharmacokinetics of enoxaparin and consequences on dose adjustment.
abstract: The use of weight-adjusted enoxaparin dosage in patients with renal failure results in increased bleeding complications. The authors investigated the impact of patient-related factors such as renal function on the pharmacokinetics of enoxaparin. Anti-Xa activity was measured in the blood of 60 patients (74 +/- 10 years, body weight 72 +/- 15 kg, men 60%, creatinine clearance 56 +/- 24 mL/min) with acute coronary syndromes receiving subcutaneous administration of enoxaparin. A population-based approach with limited sampling strategy was used. A 1-compartment model with first-order absorption and elimination best fitted the data. The mean clearance (CL/F) and distribution volume (V/F) were 0.72 L/h and 6.65 L, respectively. V/F was influenced by body weight. CL/F was mainly related to the renal function, decreasing with increasing levels of serum creatinine, and lower in women than in men. The elimination half-life was thus estimated to be 6.4 and 9.2 hours in male and female patients, respectively. The final covariate submodel was then: [Equation included in full-text article]. Maximal anti-Xa activity was predicted to rise above 1.5 IU/mL in case of mild elevation of serum creatinine according to gender and body weight. Renal function is the main factor affecting enoxaparin pharmacokinetics. In patients with decreased renal function, enoxaparin dose should be adjusted on the basis of body weight, serum creatinine, and gender to reach a target anticoagulation level assessed by maximal anti-Xa activity in steady-state conditions.
authors.affiliation: Pharmacology Department, Pitié-Salpêtrière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France. jean-sebastien.hulot@psl.ap-hop-paris.fr
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Clarisse
authors.initials: C
authors.lastname: Vantelon
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Anissa
authors.initials: A
authors.lastname: Bouzamondo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mahé
authors.forename: Annick
authors.initials: A
authors.lastname: Ankri
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Philippe
authors.initials: P
authors.lastname: Lechat
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy; D003404:Creatinine / Q000097:blood; D017984:Enoxaparin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D003404:Creatinine