Synthesis and pharmacological evaluation of conjugates of prednisolone and non-steroidal anti-inflammatory agents.
Esters of prednisolone with ibuprofen and indomethacin were prepared by coupling the 21-hydroxy moiety of the glucocorticoid to the carboxylic group of the non-steroidal anti-inflammatory agents. The local and systemic anti-inflammatory activities of the conjugates were evaluated using the cotton pellet granuloma bioassay and their topical activity evaluated by the croton oil-induced ear edema assay, in male Sprague-Dawley rats. The results indicate that these conjugates possess greater local and topical anti-inflammatory activity than prednisolone. In the subacute ear edema bioassay, the conjugates displayed no discernible untoward systemic effects, unlike prednisolone and prednisolone acetate, which elicited significant adverse systemic effects, at equipotent doses. These findings suggest that the chemical coupling of prednisolone and non-steroidal anti-inflammatory agents produced compounds with enhanced anti-inflammatory potencies and reduced systemic toxicities, particularly when administered topically.
McLean
H M
HM
Center for Antiinflammatory Research, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307.
Lee
H J
HJ
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003345:Corticosterone / Q000097:blood; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006099:Granuloma; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D011239:Prednisolone; D003345:Corticosterone; D007052:Ibuprofen; D007213:Indomethacin