Absorption, Bioavailability, and Pharmacokinetics of Tebufelone in the Rat

Autor: Rose M. Deibel, Gene O. Kinnett, Ralph W. Farmer, William K. Sietsema, Thomas H. Eichhold, Matthew Joseph Doyle, Robert E. Smyth, Maurice Edward Loomans, Gary Robert Kelm
Rok vydání: 1993
Předmět:
Zdroj: Journal of Pharmaceutical Sciences. 82:610-612
ISSN: 0022-3549
Popis: Tebufelone (NE-11740) is a member of the new di-tertbutylphenol class of anti-inflammatory agents. It exhibits good inhibitory activity against cyclooxygenase and 5-lipoxygenase in vitro. It also shows excellent anti-inflammatory activity and inhibits bone resorption in vivo in the rat adjuvant arthritis model at an oral dose level of 1 to 2 mg/kg. The absorption, bioavailability, and pharmacokinetics of tebufelone were investigated in male Sprague-Dawley rats. Tebufelone labeled with carbon-14 was administered intravenously at doses of 0.5 and 2 mg/kg and 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 radiolabel by scintillation counting and for tebufelone by a mass spectrometric method. Comparison of the total radiolabel and tebufelone areas under the curves (AUCs) of concentration of tebufelone versus time from the 2-mg/kg intravenous and 2-mg/kg oral doses indicates that tebufelone 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/kg dose levels, but the AUC of the 10-mg/kg dose exhibits a nonproportional increase, suggesting saturation of elimination processes at this higher dose.
Databáze: OpenAIRE
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