Comparison of Tebufelone Distribution in Rat Blood Plasma and Inflamed and Noninflamed Tissues following Peroral and Intravenous Administration
| Autor: | Ralph W. Farmer, Matthew Joseph Doyle, Maurice Edward Loomans, Gary Robert Kelm, Thomas H. Eichhold |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Administration Oral Biological Availability Pharmaceutical Science Inflammation Pharmacology Carrageenan Rats Sprague-Dawley Drug levels chemistry.chemical_compound Phenols Pharmacokinetics Tebufelone Animals Medicine Distribution (pharmacology) Tissue Distribution Tissue distribution business.industry Anti-Inflammatory Agents Non-Steroidal Rat blood Rats chemistry Alkynes Injections Intravenous medicine.symptom business |
| Zdroj: | Journal of Pharmaceutical Sciences. 82:847-850 |
| ISSN: | 0022-3549 |
| Popis: | It is recognized that some acidic nonsteroidal antiinflammatory drugs (NSAIDs) accumulate in the synovial fluids of inflamed joints. The distribution of tebufelone, a member of the di-tert-butylphenol class of NSAIDs, between rat plasma and paw tissues (inflamed and noninflamed) was determined. Tebufelone was administered (doses providing 80% maximal effectiveness) perorally (po, 10 mg/kg) or intravenously (i.v., 0.5 mg/kg) to Sprague-Dawley rats just prior to injection of an inflammatory adjuvant (carrageenan) into one of the hind paws. Levels of the drug were measured in plasma, inflamed paws, and noninflamed paws at prescribed times postdosing by capillary gas chromatography/stable isotope dilution mass spectrometry. Tebufelone levels, as determined from areas under the curves of concentration versus time were sevenfold (po) and 11-fold (i.v.) higher in paw tissue than in plasma. Inflamed and noninflamed tissues have equal affinity for the drug. Calculated terminal-phase half-lives of tebufelone in paw tissue were similar following i.v. and po dosing (approximately 14 h) and equivalent to the plasma half-life of the drug after po dosing (approximately 10 h). The plasma half-life determined following i.v. dosing was considerably lower (2.8 h). The anti-inflammatory activity of tebufelone appears to correlate more closely with tissue distribution profiles than plasma drug levels at the dose levels examined. |
| Databáze: | OpenAIRE |
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