Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice.
Fiche publication
Date publication
août 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NGUYEN Philippe
Tous les auteurs :
Delavenne X, Zufferey P, Baylot D, Nguyen P, Borg JY, Fontenay M, Deygas B, Mismetti P, Laporte S
Lien Pubmed
Résumé
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.
Référence
Thromb Haemost. 2010 Aug 2;104(2):252-60