Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations

Barras, Michael A., Duffull, Stephen B., Atherton, John J. and Green, Bruce (2010) Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations. Therapeutic Drug Monitoring, 32 4: 482-488. doi:10.1097/FTD.0b013e3181e64846


Author Barras, Michael A.
Duffull, Stephen B.
Atherton, John J.
Green, Bruce
Title Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 0163-4356
1536-3694
Publication date 2010-08
Sub-type Article (original research)
DOI 10.1097/FTD.0b013e3181e64846
Volume 32
Issue 4
Start page 482
End page 488
Total pages 7
Editor Gideon Koren
Michael Oellerich
Place of publication New York, NY, U.S.A.
Publisher Lippincott-Raven
Collection year 2011
Language eng
Formatted abstract
Introduction: Enoxaparin is an anticoagulant used in the treatment of thromboembolic diseases. It is a hydrophilic molecule that is, predominantly, eliminated renally with few data to support dosing for subjects with renal impairment and/or obesity. A recently conducted randomized controlled clinical trial compared individualized enoxaparin doses based on lean body weight and renal function to conventional dosing. During this trial, anti-Xa concentrations were collected using a sparse sampling design and a population pharmacokinetic model was developed to describe the data.

Methods: The current study evaluated the ability of the individualized dose to achieve and maintain anti-Xa concentrations within the therapeutic range (0.5-1.0 IU/mL) in subjects with renal impairment and/or obesity. A matched comparison of the two dosing strategies was undertaken using individual model predicted anti-Xa concentrations generated every 30 minutes to 120 hours post initiation of therapy. Concentration-time curves were generated for each subject and the proportion of time in the therapeutic, supratherapeutic, and subtherapeutic ranges were determined.

Results: When compared with conventional dosing, individualized dosing in subjects with renal impairment resulted in a significantly greater proportion of time in the therapeutic range (median [range] = 69.9% (11.3-91.8) versus 42.6% [13.9-71.4], P = 0.02) and a significantly reduced proportion of time in the supratherapeutic range (median [range] = 9.3% (0%-67.0%) versus 37.1% (0%-85.7%), P = 0.02). Although there was a trend toward a greater proportion of time in the therapeutic range in obese subjects, this did not achieve statistical significance.

Conclusions: Individualized dosing in subjects with renal impairment is more effective than conventional dosing at achieving and maintaining therapeutic anti-Xa concentrations, which could decrease the risk of bleeding events and mortality in these subjects.
Copyright © 2010 by Lippincott Williams & Wilkins
Keyword Dose-individualization
Therapeutic range
Enoxaparin
Renal disease
Obesity
NONMEM
Therapeutic drug monitoring
Acute coronary syndromes
Intravenous unfractionated heparin
Target concentration intervention
Molecular-weight heparins
Trial
Strategy
Efficacy
Disease
Obesity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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Created: Sun, 15 Aug 2010, 00:00:35 EST