 |
|
|
Celecoxib
|
|
| Systematic (IUPAC) name | |
| 4-[5-(4-methylphenyl)-3-(trifluoromethyl) pyrazol-1-yl]benzenesulfonamide |
|
| Identifiers | |
| CAS number | |
| ATC code | L01 M01 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C17H14F3N3O2S |
| Mol. mass | 381.373 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability |
40% |
| Protein binding | 97% (mainly to serum albumin) |
| Metabolism | Hepatic (mainly CYP2C9) |
| Half life | ~11 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
B3(AU) C(US) |
| Legal status |
℞ Prescription only |
| Routes | Oral |
Celecoxib (INN) (pronounced /sɛlɨˈkɒksɪb/) is a Non-steroidal anti-inflammatory drug
Celecoxib is licensed for use in osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce the number of colon and rectal polyps in patients with familial adenomatous polyposis. It was originally intended to relieve pain while minimizing the gastrointestinal adverse effects usually seen with conventional NSAIDs. In practice, its primary indication is in patients who need regular and long term pain relief: there is probably no advantage to using celecoxib for short term or acute pain relief over conventional NSAIDS
Pfizer sells Celecoxib under the brand name Celebrex. Celecoxib is not currently available as a generic in the United States, because the intellectual property is still controlled by Pfizer. However, in other countries, including India and the Philippines, it is legally available as a generic under the brand names Cobix, Celcoxx, and others.
Celecoxib is a highly selective COX-2 inhibitor
The usual adult dose of celecoxib is 100 to 200mg once or twice a day. The lowest effective dose Shou
In theory the COX-2 selectivity should result in a significantly lower incidence of gastrointestinal ulceration than traditional NSAIDs. The main body of evidence touted to support this theory were the preliminary (6 month) results of the Celecoxib Long-term Arthritis Safety Study (CLASS) as published in 2000, which demonstrated a significant reduction in the combination of symptomatic ulcers plus ulcer complications in those taking celecoxib versus Ibuprofen
Celecoxib contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs. This is in addition to the contraindication in patients with severe allergies to other NSAIDs.
There has been much concern about the possibility of increased risk for heart attack and stroke in users of NSAID drugs, particularly COX-2 selective NSAIDs such as celecoxib, since the withdrawal of the COX-2 inhibitor Rofecoxib
The cardiovascular risks of celecoxib are controversial, with apparently contradictory data produced from different clinical trials. In December 2004, "APC," the first of two Tria
Two studies on the cardiovascular risks of celecoxib and other NSAIDs were meta-analyses, published in 2006. The first of these, published in the British Medical Journal
To more conclusively establish the true cardiovascular risk profile of celecoxib, Pfizer has agreed to fund a large, randomized trial specifically designed for that purpose. The trial, centered at the Cleveland Clinic, has a planned enrollment of 20,000 high-risk patients. Celecoxib will be compared to the non-selective NSAIDS naproxen and ibuprofen.[9] Since all patients have arthritis, ethical considerations make it difficult to have a placebo group. This trial has just begun enrollment according to the Clinical Trials database, and is not scheduled to be completed until 2010. Ultimately, this trial will help answer the question as to whether Celebrex has a riskier cardiovascular profile compared to naproxen or ibuprofen.
Celecoxib was developed by G. D. Searle & Company and co-promoted by Monsanto (parent company of Searle) and Pfizer under the brand name Celebrex. Monsanto merged with Pharmacia, from which the Medical Research Division was acquired by Pfizer, giving Pfizer ownership of Celebrex. The drug was at the core of a major patent dispute that was resolved in Searle's favor (later Pfizer) in 2004. In University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004), the University of Rochester claimed that United States Pat. No. 6,048,850 (which claimed a method of inhibiting COX-2 in humans using a compound, without actually disclosing what that compound might be) covered drugs such as celecoxib. The court ruled in favor of Searle, holding in essence that the University had claimed a method requiring, yet provided no written description of, a compound that could inhibit COX-2 and therefore the patent was invalid.
After the withdrawal of rofecoxib (Vioxx) from the market in September 2004, Celebrex enjoyed a robust increase in sales. However, the results of the APC trial in December of that year raised concerns that Celebrex might carry risks similar to those of Vioxx, and Pfizer announced a moratorium on direct-to-consumer advertising of Celebrex soon afterwards. After a significant drop, sales of Celebrex have recovered, and reached $2 billion in 2006.[2] Pfizer resumed advertising Celebrex in magazines in 2006,[10] and resumed television advertising in April 2007 with an unorthodox, 2 1/2 minute advertisement which extensively discussed the adverse effects of Celebrex in comparison to other anti-inflammatory drugs. The ad drew criticism from the consumer advocacy group Public Citizen, which called the ad's comparisons misleading.[11] Pfizer has responded to Public Citizens concerns with assurances that they are truthfully advertising the risk and benefits of Celebrex as set forth by the FDA.
In late 2007, Pfizer released another US television ad for Celebrex, which also discussed Celecoxib's adverse effects in comparison to other anti-inflammatory drugs.
The role that celecoxib might have in reducing the rates of certain cancers has been the subject of many studies. However, given the side effects of anti-COX-2 on rates of heart disease, there is no current medical recommendation to use this drug for cancer reduction.
Different from cancer prevention, cancer treatment is focused on the therapy of tumors that have already formed and have established themselves inside the patient. Many studies are ongoing to determine whether celecoxib might be useful for this latter condition.[16] However, during molecular studies in the laboratory, it became apparent that celecoxib could interact with other intracellular components besides its most famous target, cyclooxygenase 2 (COX-2). The discovery of these additional targets has generated much controversy, and the initial assumption that celecoxib reduces tumor growth primarily via the inhibition of COX-2 became contentious.[17]
Certainly, the inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of celecoxib. However, whether inhibition of COX-2 also plays a dominant role in this drug’s anticancer effects is unclear. For example, a recent study with malignant tumor cells showed that celecoxib could inhibit the growth of these cells in vitro, but COX-2 played no role in this outcome; even more strikingly, the anticancer effects of celecoxib were also obtained with the use of cancer cell types that don’t even contain COX-2.[18]
Additional support for the idea that other targets besides COX-2 are important for celecoxib’s anticancer effects has come from studies with chemically modified versions of celecoxib. Several dozen analogs of celecoxib were generated with small alterations in their chemical structures.[19] Some of these analogs retained COX-2 inhibitory activity, whereas many others didn’t. However, when the ability of all these compounds to kill tumor cells in cell culture was investigated, it turned out that the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing that inhibition of COX-2 was not required for the anticancer effects.[19][20] One of these compounds, 2,5-dimethyl-celecoxib, which entirely lacks the ability to inhibit COX-2, actually turned out to display stronger anticancer activity than celecoxib itself.[21]
This article is based on an article from Wikipedia, the free encyclopedia and is available
under the terms of
GNU Free Documentation License.
In the Wikipedia there is a
list with all authors of this article
available.
Comments for Celecoxib:
No Comments found for Celecoxib