临床药物动力学和药效学的塞来昔布:选择性cyclo-oxygenase-2抑制剂。
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戴维斯NM,克劳克兰AJ,天罗,威廉姆斯公里
临床药物动力学和药效学的塞来昔布:选择性cyclo-oxygenase-2抑制剂。
Pharmacokinet。2000年3月,38 (3):225 - 42。doi: 10.2165 / 00003088-200038030-00003。
- PubMed ID
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10749518 (在PubMed]
- 文摘
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塞来昔布,非甾体类抗炎药(非甾体抗炎药),是第一个特定抑制剂的cyclo-oxygenase-2 (cox - 2)批准治疗风湿病和关节炎患者。初步数据表明,塞来昔布也有止痛剂和抗癌特性。选择性抑制cox - 2被认为导致减少非甾体抗炎药的副作用。在临床试验上消化道并发症发生率显著降低塞来昔布比传统的非选择性非甾体抗炎药(如萘普生、布洛芬、双氯芬酸)。的吸收速度celexocib适中时口服(血浆药物浓度峰值出现在2至4小时),虽然吸收的程度尚不清楚。Celexocib广泛蛋白质绑定,主要是血浆白蛋白,表观分布容积455 + / -166 l。血浆浓度时间曲线下的面积(AUC)塞来昔布的增加成比例增加口服剂量100至800毫克。塞来昔布是消除生物转化后羧酸和葡糖苷酸代谢物排出的尿液和粪便,小药(2%)是消除尿液中不变。塞来昔布是代谢主要由细胞色素P450 (CYP) 2 c9同工酶,消除半衰期约11个小时的健康人。种族差异在药物代谢和药代动力学变化对塞来昔布在老年人中已报告。 Plasma concentrations (AUC) of celecoxib appear to be 43% lower in patients with chronic renal insufficiency [glomerular filtration rate 2.1 to 3.6 L/h (35 to 60 ml/min)] compared with individuals with healthy renal function, with a 47% increase in apparent clearance. Compared with healthy controls, it has been reported that the steady-state AUC is increased by approximately 40% and 180% in patients with mild and moderate hepatic impairment, respectively. Celecoxib does not appear to interact with warfarin, ketoconazole or methotrexate; however, clinically significant drug interactions with fluconazole and lithium have been documented. As celecoxib is metabolised by CYP2C9, increased clinical vigilance is required during the coadministration of other substrates or inhibitors of this enzyme.
