Skeljo M V, Giraud A S, Yeomans N D
University of Melbourne, Department of Medicine, Western Hospital, Footscray, Victoria, Australia.
Dig Dis Sci. 1993 Nov;38(11):2038-42. doi: 10.1007/BF01297082.
The gastric toxicities of an enteric-coated formulation and conventional indomethacin were compared in rats. Both formulations were equally damaging to the mucosa, suggesting that topical damage was not the major route of injury. The importance of systemically mediated damage was further determined by gastrotoxicity dose-response curves and pyloric ligation experiments in which indomethacin was administered either orally or parenterally, or into stomach or duodenum with the pylorus occluded. Gastric damage was significantly higher in those groups that had received the drug parenterally or intraduodenally. The extent of deeper mucosal damage, assessed histologically, was greater in parenterally dosed rats. In further experiments, oral and parenteral routes of administration of two other nonsalicylate NSAIDs, naproxen and sodium diclofenac, were found to be equally damaging to the mucosa. Our results show that indomethacin-induced gastric damage, unlike aspirin injury, is mediated mainly systemically. Enteric-coating may not be a useful strategy in reducing gastric injury by nonsalicylate, nonsteroidal antiinflammatory drugs.
在大鼠中比较了肠溶制剂和常规吲哚美辛的胃毒性。两种制剂对黏膜的损伤程度相同，这表明局部损伤并非主要的损伤途径。通过胃毒性剂量反应曲线和幽门结扎实验进一步确定了全身介导损伤的重要性，在这些实验中，吲哚美辛通过口服、胃肠外给药，或在幽门闭塞的情况下注入胃或十二指肠。接受胃肠外给药或十二指肠内给药的组中胃损伤明显更高。组织学评估显示，胃肠外给药的大鼠更深层黏膜损伤的程度更大。在进一步的实验中，发现另外两种非水杨酸类非甾体抗炎药萘普生和双氯芬酸钠的口服和胃肠外给药途径对黏膜的损伤程度相同。我们的结果表明，与阿司匹林损伤不同，吲哚美辛诱导的胃损伤主要由全身介导。肠溶包衣可能不是减少非水杨酸类非甾体抗炎药所致胃损伤的有效策略。
