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Thromb Haemost 2010; 104(02): 252-260
DOI: 10.1160/TH10-02-0127
DOI: 10.1160/TH10-02-0127
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice
Financial support: The POP-A-RIX study has received funding support from the Ministère de la Santé- France- Programme Hospitalier de Recherche Clinique and was promoted by the University Hospital of Saint Etienne. The study was also supported by a grant from Fédération Hospitalière de France, Leem “Année Recherche Clinique” 2006. The first author has received the prize “jeune chercheur” from the “Société Francaise de Pharmacologie et Thérapeutique“ 2009.
Weitere Informationen
Publikationsverlauf
Received:
18. Februar 2010
Accepted after minor revision:
02. April 2010
Publikationsdatum:
24. November 2017 (online)
Summary
Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed. This study was a multicenter, prospective cohort study in consecutive orthopaedic patients treated with 2.5 mg of fondaparinux. Anti-Xa activities were recorded in 809 patients. Population parameters and inter-individual variability were estimated using NONMEM VI software. A two-compartment model with first-order absorption best described fondaparinux pharmacokinetics. Covariates partly explaining inter-individual variability were body weight, age and creatinine clearance estimated by the simplified Modification of Diet in Renal Disease formula (MDRD). A body weight less than 50 kg and moderate renal failure increased drug exposure. Although the population pharmacokinetic model of fondaparinux was described, this one requires to be validated in everyday practice.
* A list of investigators is given in the Appendix.
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