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药品详细

Sulindac(舒林酸)

化学结构式图
中文名
舒林酸
英文名
Sulindac
分子式
C20H17FO3S
化学名
2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
分子量
Average: 356.411
Monoisotopic: 356.088243305
CAS号
38194-50-2
ATC分类
M01A 未知
药物类型
small molecule
阶段
approved
商品名
Clinoril (Merck);
同义名
基本介绍

Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA’s except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

生产厂家
  • Epic pharma llc
  • Heritage pharmaceuticals inc
  • Merck research laboratories div merck co inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
ANTIINFLAMMATORY AND ANTIRHEUMATIC 消炎抗风湿;
药理
Indication For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.
Pharmacodynamics Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.
Mechanism of action Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX-1 and COX-2 which leads to the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Absorption Approximately 90% absorbed in humans following oral administration.
Volume of distribution Not Available
Protein binding At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.
Metabolism
Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Sulindac
    		Sulindac sulfide Details
    Sulindac
      		Sulindac sulfone Details
      Route of elimination Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
      Half life The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
      Clearance
      • Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
      Toxicity Acute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension.
      Affected organisms
      • Humans and other mammals
      Pathways
      Pathway Name SMPDB ID
      Smp00094 Sulindac Pathway SMP00094
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 183 °C PhysProp
      water solubility 3000 mg/L MERCK INDEX (1996); pH 7
      logP 3.42 SANGSTER (1993)
      pKa 4.7 MERCK INDEX (1996)
      Predicted Properties
      Property Value Source
      water solubility 2.51e-02 g/l ALOGPS
      logP 2.96 ALOGPS
      logP 2.93 ChemAxon
      logS -4.2 ALOGPS
      pKa (strongest acidic) 4.09 ChemAxon
      pKa (strongest basic) -6.7 ChemAxon
      physiological charge -1 ChemAxon
      hydrogen acceptor count 3 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 54.37 ChemAxon
      rotatable bond count 4 ChemAxon
      refractivity 99.56 ChemAxon
      polarizability 37.2 ChemAxon
      药物相互作用
      Drug Interaction
      Acenocoumarol The NSAID, sulindac, may increase the anticoagulant effect of acenocoumarol. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      Acetylsalicylic acid Risk of additive toxicity (e.g. bleed risk). Acetylsalicylic acid may decrease the serum concentration of sulindac. Sulindac may counteract the cardioprotective effects of acetylsalicylic acid. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Aminosalicylic Acid Risk of additive toxicity (e.g. bleed risk). Aminosalicylic acid may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Azilsartan medoxomil Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
      Bumetanide The NSAID, sulindac, decreases the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
      Cholestyramine The bile acid sequestrant, cholestyramine, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if cholestyramine is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.
      Colesevelam The bile acid sequestrant, colesevelam, may decrease the absorption of the NSAID, sulindac. Sulindac should be administered at least 1 hour before or 4 hours after colesevelam. Monitor for changes in the therapeutic and adverse effects of sulindac if colesevelam is initiated, discontinued or dose changed.
      Colestipol The bile acid sequestrant, colestipol, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if colestipol is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.
      Cyclosporine The NSAID, sulindac, may increase the nephrotoxic effect of cyclosporine. Sulindac may increase the serum concentration of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine levels and nephrotoxicity during concomitant therapy.
      Ethacrynic acid The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, ethacryninc acid.
      Furosemide The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.
      Ginkgo biloba Ginkgo biloba may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Ginseng Ginseng may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Ketorolac May cause additive or synergistic NSAID toxicities (e.g. GI bleeding, renal dysfunction, etc.). Concomitant therapy is contraindicated.
      Methotrexate The NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities.
      Pemetrexed The NSAID, sulindac, may increase the serum concentration of pemetrexed by decreasing its elimination. This interaction more prevalent in patients with mild to moderate renal insufficiency. Consider alternate therapy or monitor for pemetrexed toxicity during concomitant therapy.
      Pralatrexate NSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
      S-Adenosylmethionine S-adenosylmethionine may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Salicylate-sodium Risk of additive toxicity (e.g. bleed risk). Salicylate-sodium may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Salsalate Risk of additive toxicity (e.g. bleed risk). Salsalate may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Telmisartan Concomitant use of Telmisartan and Sulindac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
      Timolol The NSAID, Sulindac, may antagonize the antihypertensive effect of Timolol.
      Trandolapril The NSAID, Sulindac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Sulindac is initiated, discontinued or dose changed.
      Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Sulindac. Monitor for increased bleeding during concomitant thearpy.
      Warfarin The antiplatelet effects of sulindac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      食物相互作用
      Not Available

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