Tavares I A, Collins P O, Bennett A
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Aliment Pharmacol Ther. 1987 Dec;1(6):617-25. doi: 10.1111/j.1365-2036.1987.tb00647.x.
Non-steroidal anti-inflammatory drugs (NSAIDs) damage the gastric mucosa, and an important part of this effect is probably due to inhibition of prostaglandin synthesis. We have therefore studied various drugs for their ability to reduce prostaglandin and thromboxane formation by human isolated gastric mucosa. The overall relative potencies for inhibiting the endogenous production of PGE, 6-keto-PGF1 alpha and thromboxane B2 by mucosal pieces was generally: indomethacin = naproxen greater than ibuprofen greater than piroxicam; diflunisal, the prodrug sulindac, and the analgesic paracetamol usually had small or variable effects. This rank order was mainly similar to the inhibition of gastric microsomal PGE2 formation from exogenous arachidonic acid, the relative potencies being: indomethacin greater than naproxen greater than ibuprofen = piroxicam = diflunisal; again sulindac and paracetamol had little or no effect. The relative propensity of NSAIDs to cause gastric mucosal damage is controversial, but aspirin and indomethacin may be worst, and ibuprofen seems to be among the safest. Potency as an inhibitor of prostaglandin synthesis correlates better with the reported propensity for damage than does potency x dose. For reasons that are given in the discussion, this may indicate that gastric mucosal damage by NSAIDs with short or moderate half-lives is due largely to locally absorbed drug. Whereas inhibition of prostaglandin synthesis is probably the major cause of the damage, the simultaneous reduction of thromboxane formation might be advantageous for gastric mucosal integrity. Various implications arise from our hypotheses concerning the design of anti-inflammatory drugs.
非甾体抗炎药（NSAIDs）会损害胃黏膜，这种作用的一个重要部分可能是由于前列腺素合成受到抑制。因此，我们研究了多种药物对人离体胃黏膜前列腺素和血栓素生成的影响。黏膜碎片对内源性PGE、6-酮-PGF1α和血栓素B2生成的总体相对抑制效力通常为：吲哚美辛 = 萘普生＞布洛芬＞吡罗昔康；双氯芬酸、前体药物舒林酸以及镇痛药对乙酰氨基酚通常影响较小或影响不一。这个排序主要与对外源性花生四烯酸生成胃微粒体PGE2的抑制情况相似，相对效力为：吲哚美辛＞萘普生＞布洛芬 = 吡罗昔康 = 双氯芬酸；舒林酸和对乙酰氨基酚同样影响很小或无影响。NSAIDs导致胃黏膜损伤的相对倾向存在争议，但阿司匹林和吲哚美辛可能是最严重的，布洛芬似乎是最安全的之一。作为前列腺素合成抑制剂的效力与报道的损伤倾向的相关性比效力×剂量的相关性更好。出于讨论中给出的原因，这可能表明半衰期短或中等的NSAIDs对胃黏膜的损伤很大程度上是由于局部吸收的药物。虽然前列腺素合成的抑制可能是损伤的主要原因，但同时减少血栓素的生成可能对胃黏膜完整性有利。我们关于抗炎药设计的假设产生了各种影响。
