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.
PURPOSE: In absence of specific dosing guidelines, the optimal dose of low molecular weight heparins for thrombosis prophylaxis in morbidly obesepatients (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-obesepatients 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-obesepatients 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: Douglas J Eleveld; Johannes H Proost; Anthony R Absalom; Michel M R F Struys Journal: Clin Pharmacokinet Date: 2011-11-01 Impact factor: 6.447
Authors: Cynthia L Ogden; Margaret D Carroll; Lester R Curtin; Margaret A McDowell; Carolyn J Tabak; Katherine M Flegal Journal: JAMA Date: 2006-04-05 Impact factor: 56.272
Authors: A Berges; S Laporte; M Epinat; P Zufferey; E Alamartine; B Tranchand; H Decousus; P Mismetti Journal: Br J Clin Pharmacol Date: 2007-05-17 Impact factor: 4.335
Authors: Sjoerd de Hoogd; Pyry A J Välitalo; Albert Dahan; Simone van Kralingen; Michael M W Coughtrie; Eric P A van Dongen; Bert van Ramshorst; Catherijne A J Knibbe Journal: Clin Pharmacokinet Date: 2017-12 Impact factor: 6.447