Celecoxib pathways: pharmacokinetics and pharmacodynamics.
Celecoxib pathways: pharmacokinetics and pharmacodynamics.
复制标题
DOI：
10.1097/fpc.0b013e32834f94cb
复制
发表时间：
2012-04
影响因子：
2.6
通讯作者：
Klein TE
中科院分区：
文献类型：
--
作者：
Gong L;Thorn CF;Bertagnolli MM;Grosser T;Altman RB;Klein TE
塞来昔布是一种非类固醇抗炎药，具有抗炎、镇痛和解热等作用。塞来昔布已被批准用于治疗骨关节炎、类风湿性关节炎、强直性脊柱炎和急性疼痛1-3。塞来昔布在预防癌症方面也显示出很好的前景，并已被用作手术的辅助手段，以减少遗传性结肠癌易感综合征-家族性腺瘤性息肉病(FAP)4-6患者的腺瘤性结直肠息肉的数量。塞来昔布的抗炎和止痛特性源于选择性地抑制前列腺素(PG)的合成(由Ptgs2基因编码)。PTGS的两个亚型，PTGS1和Ptgs2，是具有环氧合酶(COX)和氢过氧化物酶活性的双功能酶，但它们通常被称为COX；参见(药效学部分)1，7，8。塞来昔布是NSAIDs亚类的成员，被故意设计为COX-2选择性抑制剂(pdCOX-2抑制剂)，通常被称为Coxib9，10。大多数传统的NSAID(TNSAIDs)抑制这两种COX异构体；然而，其中一些药物显示出与塞来昔布类似的COX-2选择性，尽管它们是在COX-2被发现之前开发的11。pdCOX-2抑制剂提供的抗炎作用与tNSAIDs相当，后者抑制两种COX亚型，同时降低严重胃肠道毒性的风险。
BackgroundCelecoxib is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgestic, and antipyretic properties. It is approved for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute pain 1–3. Celecoxib has also shown promise in prevention of cancer, and has been used as an adjunct to surgery to reduce the number of adenomatous colorectal polyps in patients with the hereditary colon cancer susceptibility syndrome, familial adenomatous polyposis (FAP) 4–6. The anti-inflammatory and pain-relieving properties of celecoxib result from inhibition of prostaglandin (PG) synthesis by selective inhibition of PG G/H synthase-2 (encoded by gene PTGS2). The two PTGS isoforms, PTGS1 and PTGS2, are bisfunctional enzymes with both cyclooxygenase (COX) and hydroperoxidase activities, but they are commonly referred to as COX; see (‘Pharmacodynamics’ section) 1, 7, 8. Celecoxib is a member of the subclass of NSAIDs, which were purposefully designed as COX-2-selective inhibitors (pdCOX-2 inhibitors) and that are frequently called coxibs 9, 10. Most traditional NSAIDs (tNSAIDs) inhibit both COX isoforms; however, some of them show a degree of COX-2 selectivity that is similar to that of celecoxib, although they were developed before COX-2 was discovered 11. pdCOX-2 inhibitors provide anti-inflammatory effects that are comparable with tNSAIDs that inhibit both COX isoforms while reducing the risk of serious gastrointestinal toxicity.