Absorption, bioavailability, and pharmacokinetics of tebufelone in the rat.

Abstract

Tebufelone (NE-11740) is a member of the new di-tert-butylphenol 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.

• Authors: W K Sietsema, G R Kelm, R M Deibel, M J Doyle, M E Loomans, R E Smyth, G O Kinnett, T H Eichhold, R W Farmer
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 82 Issue 6 Pg. 610-2 (Jun 1993) ISSN: 0022-3549 [Print] United States
• PMID: 8331535 (Publication Type: Journal Article)

Chemical References

• Alkynes
• Anti-Inflammatory Agents, Non-Steroidal
• Phenols
• tebufelone

Topics

• Absorption
• Administration, Oral
• Alkynes (pharmacokinetics)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics)
• Biological Availability
• Half-Life
• Injections, Intravenous
• Male
• Phenols (pharmacokinetics)
• Rats
• Rats, Sprague-Dawley