Drug Groups

withdrawn; investigational

Description

Valdecoxib was removed from the Canadian, U.S., and E.U. markets in 2005 due to concerns about possible increased risk of heart attack and stroke.

Indication

For the treatment of osteoarthritis and dysmenorrhoea

Pharmacology

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib is used for its anti-inflammatory, analgesic, and antipyretic activities in the management of osteoarthritis (OA) and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism.

Toxicity

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.

Affected Organisms

Biotransformation

Hepatic (involves CYP3A4 and 2C9)

Absorption

Oral bioavailability is 83%.

Half Life

8-11 hours

Protein Binding

98%

Elimination

Valdecoxib is eliminated predominantly via hepatic metabolism with less than 5% of the dose excreted unchanged in the urine and feces. About 70% of the dose is excreted in the urine as metabolites, and about 20% as valdecoxib N-glucuronide.

Distribution

* 86 L

Clearance

* oral cl=6 L/h
* 6 – 7 L/h [In patients undergoing hemodialysis]
* 6 – 7 L/h [healthy elderly subjects]

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