Display Settings:

Format

Send to:

Choose Destination
Br J Clin Pharmacol. 2009 Nov;68(5):700-11. doi: 10.1111/j.1365-2125.2009.03518.x.

Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events.

Author information

  • 1School of Pharmacy, University of Queensland, Brisbane, Queensland, Australia.

Abstract

AIMS:

To develop a population pharmacokinetic-pharmacodynamic model to describe the occurrence and severity of bleeding or bruising as a function of enoxaparin exposure.

METHODS:

Data were obtained from a randomized controlled trial (n = 118) that compared conventional dosing of enoxaparin (product label) with an individualized dosing regimen. Anti-Xa concentrations were sampled using a sparse design and the size, location and type of bruising and bleeding event, during enoxaparin therapy, were collected daily. A population pharmacokinetic-pharmacodynamic analysis was performed using nonlinear mixed effects techniques. The final model was used to explore how the probability of events in patients with obesity and/or renal impairment varied under differing dosing strategies.

RESULTS:

Three hundred and forty-nine anti-Xa concentrations were available for analysis. A two-compartment first-order absorption and elimination model best fit the data, with lean body weight describing between-subject variability in clearance and central volume of distribution. A three-category proportional-odds model described the occurrence and severity of events as a function of both cumulative enoxaparin AUC (cAUC) and subject age. Simulations showed that individualized dosing decreased the probability of a bleeding or major bruising event when compared with conventional dosing, which was most noticeable in subjects with obesity and renal impairment.

CONCLUSIONS:

The occurrence and severity of a bleeding or major bruising event to enoxaparin, administered for the treatment of a thromboembolic disease, can be described as a function of both cAUC and subject age. Individualized dosing of enoxaparin will reduce the probability of an event.

PMID:
19916994
[PubMed - indexed for MEDLINE]
PMCID:
PMC2791976
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing Icon for PubMed Central
    Loading ...
    Write to the Help Desk