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Population pharmacodynamic model for low molecular weight heparin nadroparin in morbidly obese and non-obese patients using anti-Xa levels as endpoint.
- Source :
- European Journal of Clinical Pharmacology; Jan2015, Vol. 71 Issue 1, p25-34, 10p, 1 Diagram, 3 Charts, 4 Graphs
- Publication Year :
- 2015
-
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) 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- THROMBOEMBOLISM prevention
BIOLOGICAL assay
BIOTRANSFORMATION (Metabolism)
BODY weight
CONFIDENCE intervals
FISHER exact test
LONGITUDINAL method
MEDICAL cooperation
OBESITY
RESEARCH
RESEARCH evaluation
STATISTICS
VEINS
DATA analysis
DATA analysis software
DESCRIPTIVE statistics
ENOXAPARIN
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00316970
- Volume :
- 71
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- European Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 100209209
- Full Text :
- https://doi.org/10.1007/s00228-014-1760-4