The Pharmacokinetics of Fondaparinux Sodium in Healthy Volunteers

Results: After a 2.5mg subcutaneous dose to young volunteers, absolute bioavail-ability was 100% and absorption was rapid and complete [peak plasma concentration (C_max) 0.34 mg/L occurred at approximately 2 hours]. Within- and total-subject variability estimates were small: 5.5 and 11.6%, respectively, for C_max and 4.4 and 17.5% for area under the concentration-time curve (AUC). Steady state was obtained after the third or fourth once-daily dose, with a 1.3-fold increase in C_max and AUC. Distribution volume (7 to 11L) was limited to blood volume. There was no evidence of metabolism. Fondaparinux sodium was almost completely excreted in urine as unchanged compound (64 to 77% of the dose was recovered at 72 hours after administration). Plasma clearance was 5.1 to 7.9 ml/min, renal clearance 4.0 to 7.9 ml/min, and the terminal half-life was 17 hours in young volunteers and 21 hours in elderly volunteers. Pharmacokinetics of fondaparinux sodium were linear in the range 2 to 8mg subcutaneously and 2 to 20mg intravenously. Pharmacokinetics observed in healthy elderly volunteers were consistent with findings in young male volunteers.