Anti-inflammatory Effects of Etodolac : Comparison with Other Non-steroidal Anti-inflammatory Drugs

The anti-inflammatory effects of etodolac (Eto) were compared with those of 6 other anti-inflammatory drugs : indomethacin (Ind), diclofenac Na (Dic), piroxicam (Pir), naproxen (Nap), ketoprofen (Ket) and aspirin (Asp). Eto inhibited carrageenin-induced edema in rats, adjuvant-induced arthritis in rats, acetic acid-induced writhing in mice and brewer's yeast-induced hyperalgesia and fever in rats. In the adjuvant arthritis test, the ED30 value (1.88mg/kg) on day 3 and ED50 values (adjuvant-injected paw : 1.18mg/kg and non-injected paw : 0.96mg/kg) on day 18 for Eto were comparable to those for Dic (2.16, 1.72 and 1.28) when given prophylactically and the ED50 values for Eto (adjuvant-injected paw : 1.61 and non-injected paw : 1.20mg/kg) were comparable to those for Ket (1.24 and 1.22) when used therapeutically. The analgesic activity of Eto (ED50 value : 3.67mg/kg) in the acetic acid-induced writhing test was greater than that of Nap (9.83) or Asp (31.6) and less than that of Ind (0.71), Dic (1.54), Pir (0.92) or Ket (1.34). In the antipyretic test, the minimum effective dose (MED : 1mg/kg) for Eto was comparable to that for Ind (1.0), Nap (1.0) or Ket (1.0). Eto was less potent in inhibiting carrageenin-induced edema (ED30 value : 6.99mg/kg) and inflammatory pain (ED50 value : 9.24mg/kg) than the other drugs (Ind : 2.32 and 3.47, Dic : 0.69 and 3.80, Pir : 1.31 and 1.94, Nap : 1.83 and 2.78, Ket : 1.12 and 0.63), except for Asp (167 and 51.8). Eto was the least ulcerogenic (UD50 value : the dose which caused ulcer action in 50% rats : 84.2mg/kg) compound among the drugs tested (Ind : 4.24, Dic : 12.7, Pir : 3.14, Nap : 42.3, Ket : 2.69, Asp : 20.8), so its safety margin (the ratio of the UD50 value to the ED30, ED50 or MED value) was greater than those of the other drugs. Thus, Eto is considered to be an effective anti-inflammatory drug with weak ulcerogenic activity.