COMPARATIVE EFFICACY AND SAFETY OF INTRAVENOUS NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN 2 ANIMAL-MODELS OF PAIN

In this study, the antinociceptive activity of five non-steroidal anti -inflammatory drugs (NSAIDs) was determined in two animal models of di fferent pain intensity and compared with their capacity to produce mot or incoordination and death. Intravenous clonixine, diclofenac, dipyro ne (metamizole), ketorolac, and piroxicam produced dose-dependent anti nociception in the acetylcholine-induced writhing test with ED(50) val ues ranging from 14 (clonixine) to 205 (dipyrone) mu mol/kg. The behav ioral responses in the 55 degrees C hot plate assay were also inhibite d in a dose-dependent manner, but significantly higher doses were requ ired to display antinociceptive activity, the ED(50) values ranging fr om 116 (clonixine) to 2,263 (dipyrone) mu mol/kg. In the writhing test , the antinociceptive effects of NSAIDs were present at doses far belo w those producing toxic effects. in contrast, their ED(50) values agai nst a more intense nociceptive stimulus approached those producing let hal effects so that the therapeutic ratios were very small, ranging fr om 1.3 (diclofenac) to 3.0 (dipyrone). The antinociceptive activity of the reference drug morphine is striking, since both types of nocicept ive responses were eliminated at doses substantially lower than those producing death (therapeutic ratios of 502 and 121). Morphine exhibite d the highest antinociceptive efficacy, followed by dipyrone, ketorola c, clonixine, and piroxicam. Diclofenac showed a more limited efficacy . These findings imply potential risks for patients treated iv with th is class of drugs and suggest caution in the use of high doses of NSAI Ds. Future development of injectable NSAID formulations should include a detailed analysis of adverse reactions following iv administration of high doses. (C) 1995 Wiley-Liss, Inc.