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药品详细

Celecoxib(塞来昔布)

化学结构式图
中文名
塞来昔布
英文名
Celecoxib
分子式
C17H14F3N3O2S
化学名
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide
分子量
Average: 381.372
Monoisotopic: 381.075882012
CAS号
169590-42-5
ATC分类
L01X 其它抗肿瘤药;M01A 未知
药物类型
small molecule
阶段
approved
商品名
Celebra;Celebrex;
同义名
celecoxib;Celocoxib;
基本介绍

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.

生产厂家
  • Gd searle llc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Malhotra S, Shafiq N, Pandhi P: COX-2 inhibitors: a CLASS act or Just VIGORously promoted. MedGenMed. 2004 Mar 23;6(1):6. Pubmed
  2. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000 Sep 13;284(10):1247-55. Pubmed
  3. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. Epub 2005 Feb 15. Pubmed
  4. Yelland MJ, Nikles CJ, McNairn N, Del Mar CB, Schluter PJ, Brown RM: Celecoxib compared with sustained-release paracetamol for osteoarthritis: a series of n-of-1 trials. Rheumatology (Oxford). 2007 Jan;46(1):135-40. Epub 2006 Jun 15. Pubmed
  5. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. Pubmed
  6. FDA label
  7. Sandberg M, Yasar U, Stromberg P, Hoog JO, Eliasson E: Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br J Clin Pharmacol. 2002 Oct;54(4):423-9. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Pyrazoles
  • Sulfonyls
  • Halogen Derivatives
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfanilamides
  • Sulfonamides
  • Imines
  • Anilines
适应症
;ANTIINFLAMMATORY AND ANTIRHEUMATIC 消炎抗风湿;Cancer 癌症;
药理
Indication For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis
Pharmacodynamics Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Celecoxib is used to treat rheumatoid arthritis, osteoarthritis, and familial adenomatous polyposis (FAP). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis. It is not known if there are any effects of celecoxib on platelets that may contribute to the increased risk of serious cardiovascular thrombotic adverse events associated with the use of celecoxib. Inhibition of PGE2 synthesis may lead to sodium and water retention through increased fluid reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by counteracting the action of antidiuretic hormone.
Mechanism of action The mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis. Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. It binds with its polar sulfonamide side chain to a hydrophilic side pocket region close to the active COX-2 binding site. Both COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane.
Absorption Well absorbed in the gastrointestinal tract. When a single dose of 200 mg is given to healthy subjects, peak plasma levels occur 3 hours after an oral dose. The peak plasma level is 705 ng/mL. Absolute bioavailability studies have not been conducted. When multiple doses are given, steady-state is reached on or before Day 5. When taken with a high fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%.
Volume of distribution

Apparent volume of distribution at steady state (Vdss/F), 200 mg single dose, healthy subjects = 429 L
Protein binding 97%, primarily to albumin and, to a lesser extent, a1-acid glycoprotein. Celecoxib is not preferentially bound to red blood cells.
Metabolism
Hepatic. Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. CYP3A4 is also involved in the hydroxylation of celecoxib but to a lesser extent. These metabolites are inactive as COX-1 or COX-2 inhibitors.

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

Substrate Enzymes Product
Celecoxib
Hydroxycelecoxib Details
Celecoxib
    		Carboxycelecoxib Details
    Celecoxib
      		Celecoxib glucuronide Details
      Route of elimination Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces. 57% of the oral dose is excreted in the feces and 27% is excreted into the urine. The primary metabolite in urine and feces was the carboxylic acid metabolite (73%). The amount of glucuronide in the urine is low.
      Half life The effective half-life is approximately 11 hours when a single 200 mg dose is given to healthy subjects. Terminal half-life is generally variable because of the low solubility of the drug thus prolonging absorption.
      Clearance

      Apparent clearance (CL/F), single oral 200 mg dose, healthy subjects = 27.7 L/hr.
      Toxicity Symptoms of overdose include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting.
      Affected organisms
      • Humans and other mammals
      Pathways
      Pathway Name SMPDB ID
      Smp00096 Celecoxib Pathway SMP00096
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 158 °C PhysProp
      water solubility Very low water solubility (3.3 mg/L) Not Available
      logP 3.9 Not Available
      Predicted Properties
      Property Value Source
      water solubility 5.03e-03 g/l ALOGPS
      logP 3.99 ALOGPS
      logP 4.01 ChemAxon
      logS -4.9 ALOGPS
      pKa (strongest acidic) 10.7 ChemAxon
      pKa (strongest basic) -0.42 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 3 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 77.98 ChemAxon
      rotatable bond count 4 ChemAxon
      refractivity 92.23 ChemAxon
      polarizability 35.2 ChemAxon
      药物相互作用
      Drug Interaction
      Acenocoumarol Celecoxib may increase the anticoagulant effect of acenocoumarol.
      Anisindione Celecoxib may increase the anticoagulant effect of anisindione.
      Azilsartan medoxomil Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
      Colesevelam Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
      Dicumarol Celecoxib may increase the anticoagulant effect of dicumarol.
      Eltrombopag Eltrombopag increases levels of Celecoxib via metabolism decrease.
      Fluconazole Fluconazole may increase the effect of celecoxib.
      Lithium The COX-2 inhibitor increases serum levels of lithium
      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.
      Rifampin Rifampin, a strong CYP2C9 inducer, may decrease the serum levels of celecoxib by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects if rifampin is initiated, discontinued or dose changed.
      Telmisartan Concomitant use of Telmisartan and Celecoxib may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
      Timolol The NSAID, Celecoxib, may antagonize the antihypertensive effect of Timolol.
      Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Celecoxib. Consider alternate therapy or monitor for changes in Celecobix therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
      Trandolapril The NSAID, Celecoxib, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Celecoxib is initiated, discontinued or dose changed.
      Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Celecoxib. Monitor for increased bleeding during concomitant thearpy.
      Tretinoin The moderate CYP2C8 inhibitor, Celecoxib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Celecoxib is initiated, discontinued to dose changed.
      Vilazodone Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). To minimize the risk of bleeding associated with this combination, consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent, such as a proton pump inhibitor for the time that combined selective serotonin reuptake inhibitor (SSRIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) is necessary.
      Warfarin Celecoxib may increase the anticoagulant effect of warfarin.
      食物相互作用
      • Take without regard to meals.
      • Taking this product with a high-fat meal will delay the Cmax, but total absorption will be increased by 10 to 20%.

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