Antipyretic activity of tebufelone (NE-11740) in man.
Tebufelone (formerly NE-11740) is a member of the new class of di-tert-butyl-phenol anti-inflammatory agents. It has previously been reported that this new agent has potent analgesic, antipyretic, and anti-inflammatory effects using in vitro, in vivo, and ex vivo experimental models. A randomized, active- and placebo- controlled double-blinded study in 120 healthy males, 20 to 55 years old, was conducted to clinically assess tebufelone's antipyretic activity. Subjects received a single peroral dose of placebo, 650 mg aspirin (ASA), or tebufelone at doses of 25, 50, 100, or 200 mg. Thirty minutes later, E. coli endotoxin (2 ng/kg) was administered intravenously. Oral temperatures were recorded at 15 minute intervals from 30 minutes post dosing to 8 hours post endotoxin administration. Areas under the temperature curves (AUCs), adjusted for baseline, were significantly lower than placebo for ASA and all but the 25 mg tebufelone groups. An AUC dose-response equation estimates 60 mg tebufelone as equivalent to 650 mg ASA, with 50 mg tebufelone not significantly greater than 650 mg ASA. Side effects, attributable to the endotoxin, included mild flu-like symptoms and were worse in the placebo group and the non-efficacious 25 mg tebufelone group. Doses of 100 and 200 mg tebufelone had onset characteristics indistinguishable from 650 mg ASA, whereas 50 mg tebufelone showed significantly slower onset while suppressing temperature for a longer period than ASA. These results provide an important early demonstration of tebufelone's biological activity in man.
Powell
J H
JH
Procter & Gamble Co., Miami Valley Laboratories Cincinnati, Ohio.
Meredith
M P
MP
Vargas
R
R
McMahon
F G
FG
Jain
A K
AK
D000328:Adult; D000480:Alkynes / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010636:Phenols / Q000494:pharmacology*
D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010636:Phenols; C064268:tebufelone; D001241:Aspirin