Population pharmacodynamic model for low molecular weight heparin nadroparin in morbidly obese and non-obese patients using anti-Xa levels as endpoint.
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...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 1; pp. 25 - 35 |
|---|---|
| Autores principales: | , , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jan2015
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103866212&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103866212 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jan2015 vid: 71 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 103866212 100209209 10.1007/s00228-014-1760-4 103866212 ppf: 25 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Population pharmacodynamic model for low molecular weight heparin nadroparin in morbidly obese and non-obese patients using anti-Xa levels as endpoint. aug: au: Diepstraten, Jeroen Janssen, Esther Hackeng, Christian Dongen, Eric Wiezer, René Ramshorst, Bert Knibbe, Catherijne affil: Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1 3435 CM Nieuwegein The Netherlands sug: subj: Heparin, Low-Molecular-Weight Administration and Dosage Heparin, Low-Molecular-Weight Pharmacodynamics Obesity Body Weight Venous Thromboembolism Prevention and Control Human Descriptive Statistics Data Analysis Software Multicenter Studies Prospective Studies Biological Assay Validity Wilcoxon Signed Rank Test Fisher's Exact Test Simulations Male Female Adult Middle Age Metabolic Clearance Rate Confidence Intervals Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: 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. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|