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.
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European Journal of Clinical Pharmacology, Springer Verlag, 2012, 68 (10), pp.1403-1410. 〈10.1007/s00228-012-1263-0〉
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Soumis le : mardi 13 août 2013 - 00:09:50
Dernière modification le : mardi 16 octobre 2018 - 01:18:23

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Xavier Delavenne, Paul Zufferey, Philippe Nguyen, Nadia Rosencher, Charles-Marc Samama, et al.. Pharmacokinetics of fondaparinux 1.5 mg once daily in a real-world cohort of patients with renal impairment undergoing major orthopaedic surgery. European Journal of Clinical Pharmacology, Springer Verlag, 2012, 68 (10), pp.1403-1410. 〈10.1007/s00228-012-1263-0〉. 〈hal-00851193〉

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