Population pharmacodynamic model for low molecular weight heparin nadroparin in morbidly obese and non-obese patients using anti-Xa levels as endpoint.

Abstract

PURPOSE:

In absence of specific dosing guidelines, the optimal dose of low molecular weight heparins for thrombosis prophylaxis in morbidly obese patients (BMI>40 kg/m(2)) remains unknown. In order to guide dosing in this patient group, a pharmacodynamics model is developed for nadroparin in morbidly obese and non-obese patients using anti-Xa levels as an endpoint, thereby characterizing the influence of excessive body weight on different pharmacodynamic model parameters.

METHODS:

Twenty-eight morbidly obese and seven non-obese patients receiving 5700 IU and 2850 IU subcutaneous (s.c.) nadroparin for surgery, respectively, were included with a mean total body weight (TBW) of 135 kg (range 72-252 kg). Up to 11 anti-Xa levels were collected from the start until 24 h after nadroparin administration. Population pharmacodynamic modelling with covariate analysis was performed using NONMEM.

RESULTS:

In a two-compartment pharmacodynamic model with baseline endogenous anti-Xa levels, the effect of nadroparin was found to be delayed and could be best described using a transit compartment. TBW was the most predictive covariate for clearance (CL=23.0 mL/min × (TBW/70)), while lean body weight (LBW) proved the most predictive covariate for central volume of distribution (V1=7.0 L × (LBW/60)).

CONCLUSIONS:

A pharmacodynamic model was developed characterizing anti-Xa levels after s.c. administration of nadroparin in patients weighing between 72 and 252 kg with TBW and LBW as the major determinants for clearance and volume of distribution, respectively.

• Authors: Jeroen Diepstraten, Esther J H Janssen, Christian M Hackeng, Eric P A van Dongen, René J Wiezer, Bert van Ramshorst, Catherijne A J Knibbe
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 71 Issue 1 Pg. 25-34 (Jan 2015) ISSN: 1432-1041 [Electronic] Germany
• PMID: 25304008 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Nadroparin

Topics

• Adult
• Anticoagulants (pharmacology)
• Factor Xa Inhibitors (blood)
• Female
• Humans
• Male
• Middle Aged
• Models, Biological
• Nadroparin (pharmacology)
• Obesity, Morbid (blood)
• Young Adult