Macrolide antibiotics as antiinflammatory agents: Roxithromycin in an unexpected role
- 52 Downloads
The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-l-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-l-arginine assay, (2) significant inhibition of λ-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.
Unable to display preview. Download preview PDF.
- A. L. Barry, C. Thornsberry and R. N. Jones,In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin and clindamycin, Antimicrob. Agents Chemoter.31, 343–345 (1987).Google Scholar
- T. Barlam and H. C. Neu,In vitro comparison of the activity of RU 28965, a new macrolide, with that of erythromycin against aerobic and anaerobic bacteria. Antimicrob. Agents Chemoter.25, 529–531 (1984).Google Scholar
- M. Campa, I. Zolfino, S. Senesi, N. Bernardini, R. Danesi, M. Ducci, M. Oleggini, R. Di Stefano, F. Mosca, A. Lazzarini and M. Del Tacca,The penetration of roxithromycin into human skin. J. Antimicrob. Chemoter.26, 87–90 (1990).Google Scholar
- J. Sasaki,Clinical evaluation of roxithromycin in odontogenic orofacial infections. J. Antimicrob. Chemoter.20 (suppl. B), 167–170 (1987).Google Scholar
- H. Makino, S. Kuzuna, T. Naka, T. Saijo and Y. Maki,Antiinflammatory, analgesic, and antipyretic activities of methyl-7-butyl-4,5,6,7-tetrahydro-3-methylamino-4-6-dioxo-5-propyl-2H-pyrazolo[3,4-d]pyrimidine-2-carboxilate (AA-2379), a novel non-acidic agent. Agents and Actions25, 385–393 (1988).PubMedGoogle Scholar
- L. M. Brand, K. L. Skare, M. E. Loomans, H. H. Reller, R. J. Schwen, D. A. Lade, R. L. Bohne, C. S. Maddin, D. P. Moorehead, R. Fanelli, C. Chiabrando, M. G. Castelli and H. H. Tai,Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345. Agents and Actions31, 329–340 (1990).PubMedGoogle Scholar
- C. J. E. Niemegeers, W. Van Bruggen, F. Awouters and P. A. J. Janssen,The effects of suprofen in rats with implanted cotton pellets. Arzeim.-Forsch. (Drug Res.)25, 1524–1526 (1975).Google Scholar
- G. A. Higgs, K. G. Mugridge, S. Moncada and J. R. Vane,Inhibition of tissue damage by the arachidonate lipoxygenase inhibitor BW7555c. Proc. Natl. Acad. Sci. USA81, 2890–2892 (1975).Google Scholar
- A. Kitchen,Methods for the assessment of drug action on cellular accumulation. InAnti-inflammatory Compounds. InClinical Pharmacology, Vol. 9 (Ed. W. R. N. Williamson) pp. 153–191, Marcel Dekker, New York 1987.Google Scholar
- L. J. Ignarro, M. E. Gold, G. M. Buga, R. E. Byrns, K. S. Wood, G. Chaudhuri and G. Frank,Basic polyamino acids rich in arginine, lysine or ornithine cause both enhancement of and refractoriness to formation of endothelium-derived nitric oxide in pulmonary artery and vein. Circ. Res.64, 315–329 (1989).PubMedGoogle Scholar
- K. Dalziel, P. J. Dykes and R. Marks,The effects of tetracycline and erythromycin in a model of acne-type inflammation. Br. J. Exp. Path.68, 67–70 (1987).Google Scholar