PHARMACOKINETICS AND TOLERABILITY OF A NEW LOW-MOLECULAR-MASS HEPARIN(RO-11) IN HEALTHY-VOLUNTEERS - A DOSE-FINDING STUDY WITHIN THE THERAPEUTIC RANGE

This paper reports on the results of a Phase I, dose-finding study wit h a new low molecular mass heparin (LMMH) called RO-11. The study focu sed on pharmacokinetics, dose-effect relationship and on tolerability of three single subcutaneous (SC) doses within the therapeutical range . After the injection of 7,500, 9,000 and 12,500 anti-FXa IU, the anti -FXa effect peaked between 3-6 h and showed a dose-dependent response. The absorption and elimination were first-order processes and the lon g half-life (>5 h) kept constant after increasing doses. The compound was tolerated very well and no clinically relevant prolongation of APT T, prothrombin and thrombin clotting tests was observed. At the dose o f 7,500 IU, which corresponded to 110 anti-FXa IU/Kg, RO-11 exerted an ti-FXa effect for at least 18-20 h. We recommend using this dose in a single SC injection, to evaluate the efficacy and safety of RO-11 in t he initial treatment of DVT or PE.