Whittle Brendan J R
William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
Curr Opin Pharmacol. 2004 Dec;4(6):538-45. doi: 10.1016/j.coph.2004.08.003.
After a decade of intense pharmacological and drug development activity by the pharmaceutical industry, compounds derived from two key strategies for reducing gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) have been subjected to rigorous clinical appraisal. Despite the undoubted therapeutic and commercial success of the selective cyclooxygenase (COX)-2 inhibitors, known as the coxibs, with second-generation compounds already approved and launched, some concerns over their full gastrointestinal profile still linger, while the cardiovascular safety of this class has become a key issue. Likewise, Phase II evaluation of compounds incorporating a nitric oxide (NO)-donating moiety into standard NSAIDs (the NO-NSAIDs or CINODs) has created recent controversy over the full clinical profile of these compounds. Other approaches such as NO-COX-2 inhibitors and dual COX-lipoxygenase inhibitors are already warranting interest. It might therefore be too early to predict the eventual winning strategy for safer anti-inflammatory drugs.
在制药行业经过十年的高强度药理和药物研发活动后，源自两种减轻非甾体抗炎药（NSAIDs）胃肠道副作用关键策略的化合物已接受了严格的临床评估。尽管被称为昔布类的选择性环氧化酶（COX）-2抑制剂在治疗和商业上取得了毋庸置疑的成功，第二代化合物已获批上市，但对其完整胃肠道情况仍存在一些担忧，而这类药物的心血管安全性已成为一个关键问题。同样，将一氧化氮（NO）供体部分引入标准NSAIDs的化合物（NO-NSAIDs或CINODs）的II期评估，最近引发了关于这些化合物完整临床情况的争议。其他方法，如NO-COX-2抑制剂和双重COX-脂氧合酶抑制剂，已经引起了人们的兴趣。因此，预测更安全抗炎药物的最终成功策略可能为时过早。
