Ur-9825 is a new triazole class, with a potent broad espectrum antifungal activity. It is expected to be effective in treating patients suffering from all of the key opportunistic fungal infections including aspergillosis. A first-time-in-man, phase I, double-blind, randomised, placebo controlled, single rising dose study was conducted to evaluate the safety and pharmacokinetic profile of unchanged UR-9825. Seventy-two healthy volunteers were consecutively enrolled in-groups of 8 and randomly assigned to receive UR-9825 or placebo. The following dose levels were studied: 5, 10, 20, 40, 80, 160, 240, 320 and 400 mg. All subjects gave their informed consent, and the study was approved by the Regional Ethical Committee. Ur-9825 was very well tolerated at all dose levels an no serious adverse effects were reported. Furthermore, no clinical significant trends in safety parameters were noted in vital signs, ECGS and labatory tests, UR-9825 is rapidly absorbed reaching Cmax values at 2-4 h and widely distributed throughout bodyfluids and the apparent Vd/f is about 5 L/kg. There is a wide inter-subject variability in the elemination parameters of UR-9825. The absorption rate (Cmax) and extension (AUC) of UR-9825 was dose proportional for lower-medium doses (5 to 80 mg), with a range of mean terminal half-life between 30 h and 56h. A non-liniar pharmacokinetics trend at higher doses was observed due to probalbe saturation of the metabolism process. Further studies are needed to confirm these preliminary results.
Full conference title:
6th Congress of the European Confederation of Medical Mycology Societies
- ECMM 6th (2000)