Acute studies on safety index of nonsteroidal anti-inflammatory drugs in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation. Their use is frequently limited by gastrointestinal side effects, ranging from dyspeptic symptoms to life threatening bleeding or perforations of gastroduodenal ulcers. The present study mainly aimed to establish a safety index of NSAIDs in experimental animals. Safety index is based on the ratio of ulcerogenic dose (UD50) and anti-inflammatory dose (ED50). The safety index of preferential COX-2 inhibitor (nimesulide, meloxicam) was investigated using carrageenan-induced paw oedema and acute ulcerogenic model in rats, compared with the classical NSAIDs (naproxen, indomethacin). Meloxicam was found to be the most potent NSAID (ED50 1.07 mg/kg, p.o.) followed by nimesulide (2.42 mg/kg, p.o.), indomethacin (2.72 mg/kg, p.o.) and naproxen (6.82 mg/kg, p.o.) after 240 min of carrageenan challenge. In acute ulcerogenic study naproxen, indomethacin and meloxicam were found to be ulcerogenic at lower doses (UD50 14.0, 3.80 and 3.21 mg/kg, p.o.) in comparison to nimesulide (UD50 24.52 mg/kg, p.o.). Meloxicam, naproxen and indomethacin also produced damage to gastric epithelium (disruption of mucus layer and damage to parietal cells) at ED50 dose level when it was viewed under scanning electron microscope, but nimesulide did not distrub gastric mucosal integrity at ED50 dose. Based on the safety index (Ulcerogenic dose50 /Effective anti-inflammatory dose50) the order of safety of these agents was nimesulide > meloxicam > naproxen > indomethacin.