ABSORPTION, BIOAVAILABILITY, AND PHARMACOKINETICS OF TEBUFELONE IN THE RAT

Tebufelone (NE-11740) is a member of the new di-tertbutylphenol class of anti-inflammatory agents. It exhibits good inhibitory activity agai nst cyclooxygenase and 5-lipoxygenase in vitro. It also shows excellen t anti-inflammatory activity and inhibits bone resorption in vivo in t he rat adjuvant arthritis model at an oral dose level of 1 to 2 mg/kg. The absorption, bioavailability, and pharmacokinetics of tebufelone w ere investigated in male Sprague-Dawley rats. Tebufelone labeled with carbon-14 was administered intravenously at doses of 0.5 and 2 mg/kg a nd perorally at doses of 2 and 10 mg/kg to fasted rats. Plasma samples taken from the rats at timed intervals were analyzed for total radiol abel by scintillation counting and for tebufelone by a mass spectromet ric method. Comparison of the total radiolabel and tebufelone areas un der the curves (AUCs) of concentration of tebufelone versus time from the 2-mg/kg intravenous and 2-mg/kg oral doses indicates that tebufelo ne is completely absorbed and 100% bioavailable at this dose level in the rat. The AUCs are a linear function of dose at the 0.5- and 2-mg/k g dose levels, but the AUC of the 10-mg/kg dose exhibits a nonproporti onal increase, suggesting saturation of elimination processes at this higher dose.