Wallace J L, Reuter B K, McKnight W, Bak A
Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
J Clin Gastroenterol. 1998;27 Suppl 1:S28-34. doi: 10.1097/00004836-199800001-00006.
Selective inhibitors of the "inducible" isoform of cyclooxygenase (COX-2) have been suggested to be effective analgesic and anti-inflammatory drugs while sparing the gastrointestinal (GI) tract of injury. There is some experimental and early clinical evidence to support this hypothesis. However, some important questions remain regarding the utility of selective COX-2 inhibitors. For example, estimates of the selectivity of COX-2 inhibitors based on in vitro studies are likely to be poor predictors of selectivity in vivo. Efficacy with selective blockade of COX-2 may be inferior to that achieved with combined inhibition of COX-1 and COX-2. Furthermore, in situations in which there is inflammation or ulceration in the GI tract, COX-2 produces prostaglandins that are essential for repair. In these circumstances, inhibition of COX-2 leads to delay of ulcer healing and exacerbation of inflammation. Some caution should therefore be exercised before the theory is fully accepted that selective COX-2 inhibitors are effective anti-inflammatory drugs that spare the GI tract of injury.
环氧化酶（COX）-2“诱导型”同工型的选择性抑制剂被认为是有效的镇痛和抗炎药物，同时可避免胃肠道损伤。有一些实验和早期临床证据支持这一假设。然而，关于选择性COX-2抑制剂的效用仍存在一些重要问题。例如，基于体外研究对COX-2抑制剂选择性的估计可能无法很好地预测其体内选择性。选择性阻断COX-2的疗效可能不如联合抑制COX-1和COX-2所达到的疗效。此外，在胃肠道存在炎症或溃疡的情况下，COX-2会产生对修复至关重要的前列腺素。在这些情况下，抑制COX-2会导致溃疡愈合延迟和炎症加剧。因此，在选择性COX-2抑制剂是能避免胃肠道损伤的有效抗炎药物这一理论被完全接受之前，应谨慎行事。
