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

• Published in: European journal of clinical pharmacology 2012-10, Vol.68 (10), p.1403-1410
• Main Authors: Delavenne, Xavier, Zufferey, Paul, Nguyen, Philippe, Rosencher, Nadia, Samama, Charles-Marc, Bazzoli, Céline, Mismetti, Patrick, Laporte, Silvy
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anticoagulants; Anticoagulants - administration & dosage; Anticoagulants - blood; Anticoagulants - pharmacokinetics; Area Under Curve; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cohort Studies; Drug Administration Schedule; Drug dosages; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney - drug effects; Kidney - metabolism; Kidney diseases; Male; Mathematics; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Orthopedic Procedures - methods; Orthopedics; Pharmacokinetics and Disposition; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polysaccharides - administration & dosage; Polysaccharides - blood; Polysaccharides - pharmacokinetics; Renal failure; Renal Insufficiency - blood; Renal Insufficiency - metabolism; Risk factors; Statistics; Statistics Theory; Venous Thromboembolism - prevention & control
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-012-1263-0

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