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

British Journal of Clinical Pharmacology
Michael A BarrasBruce Green

Abstract

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

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Citations

Nov 18, 2011·European Journal of Clinical Pharmacology·Philipp Hoffmann, Frieder Keller
Nov 28, 2012·Clinical Pharmacokinetics·Ines PauleMichel Tod
Mar 28, 2012·Clinical Pharmacokinetics·Margreke J E BrillCatherijne A J Knibbe
Sep 17, 2013·British Journal of Clinical Pharmacology·Stephen B Duffull, Daniel F B Wright
May 6, 2010·Pharmacoepidemiology and Drug Safety
Jun 26, 2015·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Matthew ZuckermanKavita M Babu
Jun 12, 2018·Journal of Evaluation in Clinical Practice·Jeffrey K AronsonJon Williamson
Jan 13, 2021·Journal of the American Geriatrics Society·Melissa BendayanJonathan Afilalo

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