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
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
- 4uOrtho LLC
- Apotheca Inc.
- AQ Pharmaceuticals Inc.
- A-S Medication Solutions LLC
- Blenheim Pharmacal
- Bryant Ranch Prepack
- Cardinal Health
- Direct Pharmaceuticals Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- GD Searle LLC
- H.J. Harkins Co. Inc.
- Innoviant Pharmacy Inc.
- Keltman Pharmaceuticals Inc.
- Lake Erie Medical and Surgical Supply
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Physicians Total Care Inc.
- Prepackage Specialists
- Rebel Distributors Corp.
- Redpharm Drug
- Resource Optimization and Innovation LLC
- Sandhills Packaging Inc.
- Southwood Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Rx Usa
- Vangard Labs Inc.
参考
Synthesis Reference | Not Available |
General Reference |
|
剂型
规格
化合物类型
Type | small molecule |
Classes |
|
Substructures |
|
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.
|
||||||||||||||||
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 |
|
||||||||||||||||
Pathways |
|
理化性质
Properties | |||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
State | solid | ||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
|
||||||||||||||||||||||||||||||||||||||||||
Predicted Properties |
|
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%.