Disease relevance of NE 11740

• Hepatocellular hypertrophy was observed in only a single tebufelone-treated dog (50 mg/kg) [1].

High impact information on NE 11740

• The addition of the CO/5-LO inhibitor 2 h after LPS stimulation, however, did not interfere with IL 1 beta synthesis, suggesting that tebufelone interacts with an early event(s) in the activation of PBMC [2].
• We examined the effect of tebufelone, a dual cyclooxygenase (CO)/5-lipoxygenase (LO) inhibitor, on the synthesis, secretion and gene expression of interleukin (IL) 1 beta and tumor necrosis factor (TNF)-alpha by human peripheral blood mononuclear cells (PBMC) [2].
• Transcription, translation and secretion of interleukin 1 and tumor necrosis factor: effects of tebufelone, a dual cyclooxygenase/5-lipoxygenase inhibitor [2].
• In conclusion, we have demonstrated that tebufelone enhances IL 1 (alpha and beta) and TNF-alpha synthesis at concentrations which suppress leukotriene formation [2].
• The greatest increase in CYP2B11 markers produced by tebufelone treatment ranged from 2- to 3-fold, whereas the increase in CYP3A12 markers ranged from 5- to 10-fold [1].

Biological context of NE 11740

• Absorption, bioavailability, and pharmacokinetics of tebufelone in the rat [3].
• Interspecies scaling of tebufelone pharmacokinetic data and application to preclinical toxicology [4].
• The analysis suggests that doses producing tebufelone plasma levels above a certain threshold AUC and duration of exposure to parent tebufelone are associated with increased risks of hepatic effects [4].
• The anti-inflammatory activity of tebufelone appears to correlate more closely with tissue distribution profiles than plasma drug levels at the dose levels examined [5].

Anatomical context of NE 11740

• Comparison of tebufelone distribution in rat blood plasma and inflamed and noninflamed tissues following peroral and intravenous administration [5].
• Electron microscopic evaluation, however, revealed marked dose-dependent increases in smooth endoplasmic reticulum in all of the tebufelone treatment groups [1].
• The purpose of the present study was to assess the effects of tebufelone on hepatocyte ultrastructure and hepatic cytochromes p450 (P450s) in the beagle dog after 2 weeks of oral administration at dose levels of 0, 5, 15, 50, and 100 mg/kg/day (N = 1/sex/dose level) [1].

Associations of NE 11740 with other chemical compounds

• Determination of leukotriene B4 in human plasma by gas chromatography using a mass selective detector and a stable isotope labelled internal standard. Effect of NE-11740 on arachidonic acid metabolism [6].

Gene context of NE 11740

• For IL 1 beta and TNF-alpha, basal and stimulated (4 h post LPS) mRNA levels were not increased by tebufelone, despite a concomitant increase in the synthesis of IL 1 beta [2].

Analytical, diagnostic and therapeutic context of NE 11740

• Long-term performance of a gas chromatography/tandem mass spectrometry assay for tebufelone in plasma [7].
• 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 [3].
• Determination of tebufelone (a new anti-inflammatory drug) strength and stability in bulk drug, dosage formulations and feed admixtures by reversed-phase high-performance liquid chromatography [8].

References