Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice

Xavier Delavenne; Paul Zufferey; Denis Baylot; Philippe Nguyen; Jeanne-Yvonne Borg; Michaela Fontenay; Beatrice Deygas; Patrick Mismetti; Silvy Laporte; for the GETHCAM study group and POP-A-RIX investigators

doi:10.1160/TH10-02-0127

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(02): 252-260
DOI: 10.1160/TH10-02-0127

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice

Xavier Delavenne

¹Thrombosis Research Group (EA 3065), University Jean Monnet, Saint-Etienne, France

²Clinical Pharmacology Dept., University Hospital, Saint-Etienne, France

,

Paul Zufferey

¹Thrombosis Research Group (EA 3065), University Jean Monnet, Saint-Etienne, France

³Anesthesiology and Intensive Care Dept., University Hospital, Saint-Etienne, France

,

Denis Baylot

⁴Clinique Mutualiste de Saint-Etienne, France

,

Philippe Nguyen

⁵Central Hematology Laboratory, Robert Debré Hospital, Reims, France

,

Jeanne-Yvonne Borg

⁶Hemostasis Unit, University Hospital of Rouen, France

,

Michaela Fontenay

⁷Hematology Laboratory, Cochin Hospital, Paris, France

,

Beatrice Deygas

²Clinical Pharmacology Dept., University Hospital, Saint-Etienne, France

⁸Inserm, CIE3, Saint-Etienne, France

,

Patrick Mismetti

¹Thrombosis Research Group (EA 3065), University Jean Monnet, Saint-Etienne, France

²Clinical Pharmacology Dept., University Hospital, Saint-Etienne, France

,

Silvy Laporte

¹Thrombosis Research Group (EA 3065), University Jean Monnet, Saint-Etienne, France

²Clinical Pharmacology Dept., University Hospital, Saint-Etienne, France

⁸Inserm, CIE3, Saint-Etienne, France

,

for the GETHCAM study group and POP-A-RIX investigators

› Author Affiliations

Abstract

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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.

Keywords

Fondaparinux - orthopedic surgery - pharmacokinetics - simulations

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References

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