Objective: This study was designed to clarify the factors affecting the efficacy, adverse events, and pharmacokinetics of fondaparinux in Japanese patients undergoing artificial knee replacement surgery.
Materials and methods: Fondaparinux (1.5 mg/d) was administered subcutaneously to patients (n = 30) at 24 hours after surgery, and blood samples were taken at various time points thereafter. Venous thromboembolism (VTE), presence of bleeding, and pharmacokinetics were evaluated. Multivariate analysis and population pharmacokinetic analysis were performed to detect factors that necessitated withdrawal of fondaparinux and individual differences in its pharmacokinetics.
Results: VTE was observed in 9 patients (3 for whom administration was continued and 6 for whom withdrawal was necessary). The maximum plasma concentration of fondaparinux was found to be a significant factor determining withdrawal of the drug. Population pharmacokinetic analysis demonstrated that individual renal function and body weight were significant factors associated with apparent clearance and volume of distribution, respectively.
Conclusions: A high maximum plasma concentration of fondaparinux may result in subcutaneous hemorrhage, necessitating withdrawal of fondaparinux administration. The patient's kidney function and body weight also contribute to individual differences in pharmacokinetics. We recommend considering an adjustment to the dose of fondaparinux based on body weight in patients undergoing artificial knee replacement surgery. .