Pharmacokinetics of fondaparinux 1.5 mg once daily in a real-world cohort of patients with renal impairment undergoing major orthopaedic surgery.

Abstract

PURPOSE:

Fondaparinux, a selective activator factor X (factor Xa) inhibitor, is effective and safe for preventing venous thromboembolism after major orthopaedic surgery (MOS) at the once-daily subcutaneous dose of 2.5 mg. As the drug is mainly eliminated by the kidneys, a reduced dosage (1.5 mg once daily) was developed for patients with renal impairment.

METHODS:

We studied the pharmacokinetics (PK) of this dosage regimen using data from a real-world cohort of 442 patients with renal impairment (creatinine clearance 20-50 ml/min) undergoing MOS. Data were analysed using NON-linear Mixed Effect Modelling software (NONMEM) software. Fondaparinux PK was modelled using a two-compartment model with first-order absorption.

RESULTS:

This analysis confirmed the relationship between renal function and fondaparinux PK profiles. The mean predicted steady-state area under the plasma concentration time curve, peak and trough plasma concentrations of fondaparinux were lower by 15.6 %, 13.0 % and 10.3 %, respectively, in patients with renal impairment treated with 1.5 mg compared with patients with normal renal function treated with 2.5 mg (p < 0.01).

CONCLUSION:

Although administration of 1.5 mg fondaparinux in patients with renal impairment resulted in a predicted exposure slightly lower than that achieved with 2.5 mg in patients with normal renal function, fondaparinux 1.5 mg is a valuable thromboprophylactic option in MOS patients with renal impairment who are at risk of bleeding.

• Authors: Xavier Delavenne, Paul Zufferey, Philippe Nguyen, Nadia Rosencher, Charles-Marc Samama, Céline Bazzoli, Patrick Mismetti, Silvy Laporte, PROPICE Study Group
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 68 Issue 10 Pg. 1403-10 (Oct 2012) ISSN: 1432-1041 [Electronic] Germany
• PMID: 22447298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Polysaccharides
• Fondaparinux

Topics

• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Cohort Studies
• Drug Administration Schedule
• Factor Xa Inhibitors
• Female
• Fondaparinux
• Humans
• Kidney (drug effects, metabolism)
• Male
• Orthopedic Procedures (methods)
• Polysaccharides (administration & dosage, blood, pharmacokinetics)
• Renal Insufficiency (blood, metabolism)
• Venous Thromboembolism (prevention & control)