Comparison of the anti-inflammatory activity and gastrointestinal irritancy of nabumetone, ibuprofen, and diclofenac in rats following chronic administration.
Nabumetone, a novel nonsteroidal anti-inflammatory drug, has aroused considerable interest due to mounting evidence suggesting a diminished potential for causing gastrointestinal mucosal irritancy. In the present study, rats were administered equally effective oral suspensions of either nabumetone (79mg/kg), ibuprofen (88mg/kg), diclofenac (11.5mg/kg), or a control suspension (n = 8 or 9 per group) daily for one month and subsequently assessed for various indices of anti-inflammatory activity, gastrointestinal irritancy, and prostaglandin inhibitory activity. Daily doses were five times the ID25 for carrageenan-induced paw inflammation as obtained in previous studies. At the end of the administration period, nabumetone maintained effective antiinflammatory activity, but was devoid of gastrointestinal irritancy. In contrast, ibuprofen and diclofenac were associated with marked and significant gastrointestinal mucosal damage. The findings of the present study support published preclinical and clinical studies establishing nabumetone as an effective anti-inflammatory agent with a favourable gastrointestinal safety profile.
Melarange
R
R
SmithKline Beecham Pharmaceuticals, Research and Development Technologies, Harlow, UK.
Blower
P
P
Spangler
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002074:Butanones / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D002432:Cecum / Q000737:chemistry; D004008:Diclofenac / Q000494:pharmacology* / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects*; D004334:Drug Administration Schedule; D005753:Gastric Mucosa / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006242:Haptoglobins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D007052:Ibuprofen / Q000494:pharmacology* / Q000633:toxicity; D007082:Ileum / Q000187:drug effects; D008297:Male; D000077430:Nabumetone; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D006242:Haptoglobins; D006454:Hemoglobins; D004008:Diclofenac; D015121:6-Ketoprostaglandin F1 alpha; D002351:Carrageenan; D000077430:Nabumetone; D007052:Ibuprofen