These observations paved the way for the development of fondaparinux. 1.3.2 Pharmacology: A synthetic analog of the AT-binding pentasaccharide found in heparin and LMWH was prepared and its structure modi ed so as to increase its af nity for AT, thereby increasing its speci c activity and its half-life. The resulting syn- thetic pentasaccharide, fondaparinux, has a molec- ular weight of 1,728. Its speci c anti-Xa activity is higher than that of LMWH (about 700 units/mg and 100 units/mg, respectively), and its half-life after sub- cutaneous injection is longer than that of LMWH (17 h and about 4 h, respectively). The use of LMWH as the reference preparation for determining the measured anti-Xa activity of fondaparinux is prob- lematic.196,197 As a result, fondaparinux levels should only be determined using assays that use known fondaparinux concentrations to generate their stan- dard curve. Fondaparinux binds to AT and produces a confor- mational change at the reactive site of AT that enhances its reactivity with factor Xa.198 AT then forms a covalent complex with factor Xa. Fonda- parinux is released from AT and is available to acti- vate additional AT molecules. Because it is too short to bridge AT to thrombin, fondaparinux does not increase the rate of thrombin inhibition by AT. The pharmacokinetic properties and metabolism of fondaparinux have been studied in healthy volun- teers.199,200 After subcutaneous injection, fondaparinux is rapidly and completely absorbed. A steady state is reached after the third or fourth once-daily dose, and fondaparinux is excreted unchanged in the urine. The terminal half-life is 17 h in young subjects and 21 h in elderly volunteers. 