Evaluation of the pharmacological properties and clinical results of the synthetic XXXX (fondaparinux).

@entity1 @entity23868 @entity548 @entity1229 @entity27408 @entity177 @entity1459 @entity1031 @entity1129 @entity1211 @entity583 @entity5582 @entity6236 @entity11942
Fondaparinux (Arixtra) is the first of a new class of selective indirect @entity5582 -dependent factor Xa inhibitors, which inhibits thrombin generation. Fondaparinux is a completely synthetic @entity23868 . It is a single molecular entity with a well-defined pharmacological target. Fondaparinux has nearly complete bioavailability after subcutaneous injection. The pharmacokinetics of fondaparinux appears predictable and consistent. The peak plasma level is obtained about 2 h after the subcutaneous injection, indicating that a rapid onset of antithrombotic activity is obtained on initiation of treatment. The elimination half-life is about 17 h and it is dose-independent, which allows a convenient once-daily dosing regimen. Fondaparinux is eliminated exclusively by the kidneys. Thus, the estimation of the renal function especially in elderly @entity1 is important for the treatment with @entity27408 , whereas it is contraindicated in @entity1 with severe @entity177 . Phase II clinical studies have identified a subcutaneous dose of 2.5 mg once daily for prophylaxis of @entity1211 in @entity1 undergoing major orthopaedic surgery. Four phase-III clinical trials using bilateral phlebography for the diagnosis of @entity11942 , demonstrated a combined 50% relative risk reduction of asymptomatic venous @entity1031 in orthopaedic surgery @entity1 in comparison to the low-molecular-weight heparin (LMWH) enoxaparin. @entity548 for fondaparinux were either comparable or higher than those for LMWH but the authors did not judge that the increased bleeding was clinically relevant. A dose ranging study led to the selection of the dose of 7.5 mg at a single daily subcutaneous injection as optimal for the treatment of VTE. In two phase III clinical trials, the dose of 7.5 mg/day is expected to be as efficacious and safe as heparin for the treatment of @entity11942 or PE, respectively. Phase II studies show that the efficacy-to-safety ratio of fondaparinux in the treatment of @entity1459 or as an adjunct to thrombolysis in acute @entity583 is promising. These results demonstrated that a single anti-Xa agent devoid of @entity5582 activity is a potent antithrombotic drug. Fondaparinux has obtained FDA and European health authorities approval. Its use on a large scale will allow the evaluation of its efficacy and tolerance in the daily clinical practice. Chemical modifications of the original synthetic @entity23868 increase the affinity to @entity1129 resulting in a more potent inhibition of @entity6236 and longer half-life. Idraparinux is the first of these new oligosaccharides that we named "meta-pentasaccharides." After subcutaneous injection the half-life of idraparinux is about 80 h allowing a single injection per week. A dose-finding study has established the optimal dose given once a week to be compared with @entity1229 for the treatment of @entity11942 .
