Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice.
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.
Thrombosis Research Group EA 3065, University Jean Monnet, Saint-Etienne, France. xavier.delavenne@chu-st-etienne.fr
Xavier
X
Delavenne
Paul
P
Zufferey
Denis
D
Baylot
Philippe
P
Nguyen
Jeanne-Yvonne
JY
Borg
Michaela
M
Fontenay
Beatrice
B
Deygas
Patrick
P
Mismetti
Silvy
S
Laporte
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001835:Body Weight; D003198:Computer Simulation; D003404:Creatinine / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077425:Fondaparinux; D005602:France; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D019637:Orthopedic Procedures / Q000009:adverse effects; D011134:Polysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies; D015203:Reproducibility of Results; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D055815:Young Adult
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D003404:Creatinine; D000077425:Fondaparinux