Absorption, bioavailability, and pharmacokinetics of tebufelone in the rat.
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.
Sietsema
W K
WK
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239-8707.
Kelm
G R
GR
Deibel
R M
RM
Doyle
M J
MJ
Loomans
M E
ME
Smyth
R E
RE
Kinnett
G O
GO
Eichhold
T H
TH
Farmer
R W
RW
D000042:Absorption; D000284:Administration, Oral; D000480:Alkynes / Q000493:pharmacokinetics*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001682:Biological Availability; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010636:Phenols / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010636:Phenols; C064268:tebufelone