Davies N M, Watson M S
Faculty of Medicine, Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Clin Pharmacokinet. 1997 Jun;32(6):437-59. doi: 10.2165/00003088-199732060-00002.
Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the indene acetic acid class. The absorption of sulindac is rapid when given orally. Sulindac is reversibly metabolised to sulindac sulphide which has anti-inflammatory and analgesic properties and is irreversibly metabolised to sulindac sulphone which has been suggested to possess antiproliferative effects against tumours. Sulindac and its sulphide and sulphone metabolites bind extensively to plasma albumin. Sulindac is eliminated following bio-transformation; sulindac and sulindac sulphone and their respective glucurooconjugated metabolites are excreted in urine; however only a small amount of the sulindac sulphide metabolite is eliminated in urine. Following long term twice daily administration both sulindac and its metabolites accumulate in plasma. Both patients with cirrhosis and the elderly demonstrate elevated concentrations of all species upon long term sulindac administration as compared with a single dose. The disposition of sulindac and its metabolites may be tied to renal function. In end-stage renal disease, increased free fractions of all species and accumulation of the sulphide and sulphone metabolites, and to a lesser extent sulindac, occurs. Significant drug interactions have been demonstrated for dimethylsulphoxide, cyclosporin, furosemide (frusemide), hydrochlorothiazide, methotrexate and cholestyramine.
舒林酸是茚乙酸类非甾体抗炎药（NSAID）。口服时舒林酸吸收迅速。舒林酸可逆性代谢为具有抗炎和镇痛特性的舒林酸硫化物，不可逆性代谢为据认为对肿瘤具有抗增殖作用的舒林酸砜。舒林酸及其硫化物和砜代谢物与血浆白蛋白广泛结合。舒林酸经生物转化后被清除；舒林酸、舒林酸砜及其各自的葡萄糖醛酸结合代谢物经尿液排泄；然而，尿液中仅排出少量舒林酸硫化物代谢物。长期每日两次给药后，舒林酸及其代谢物在血浆中蓄积。与单次给药相比，肝硬化患者和老年人长期服用舒林酸后，所有成分的浓度均升高。舒林酸及其代谢物的处置可能与肾功能有关。在终末期肾病中，所有成分的游离分数增加，硫化物和砜代谢物蓄积，舒林酸的蓄积程度较轻。已证实二甲亚砜、环孢素、呋塞米（速尿）、氢氯噻嗪、甲氨蝶呤和考来烯胺存在显著的药物相互作用。
