title: Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety.
abstract: OBJECTIVE
  To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination.
  
  
  METHODS
  Retrospective medical record review.
  
  
  METHODS
  1000-bed tertiary care teaching centre.
  
  
  METHODS
  Hospitalized patients that received enoxaparin by CI during a 2-year period.
  
  
  METHODS
  None.
  
  
  METHODS
  Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance.
  
  
  RESULTS
  Sixty-seven patients received enoxaparin by CI of which 61.2% were in the ward and 38.8% in the ICU. The average initial rate and duration of infusion were 5.2 mg/h and 5.6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0.64 +/- 0.34 L/h, 10.6 +/- 1.55 L and 1.01 +/- 0.39 L/h, 9.08 +/- 1.17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0.0005; P = 0.8916).
  
  
  CONCLUSIONS
  This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination.
authors.affiliation: Cleveland Clinic Foundation, USA. KaneSL@msx.upmc.edu
authors.forename: S L
authors.initials: SL
authors.lastname: Kane-Gill
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: M B
authors.initials: MB
authors.lastname: Bobek
authors.forename: R R
authors.initials: RR
authors.lastname: Bies
authors.forename: M C
authors.initials: MC
authors.lastname: Pruchnicki
authors.forename: J F
authors.initials: JF
authors.lastname: Dasta
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D003404:Creatinine / Q000378:metabolism*; D016903:Drug Monitoring; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D065427:Factor Xa Inhibitors; D005260:Female; D006746:Hospital Bed Capacity, 500 and over; D006761:Hospitals; D006785:Hospitals, University; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D016347:Medical Records Systems, Computerized; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism* / Q000503:physiopathology; D012189:Retrospective Studies
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D003404:Creatinine