Sign Out
Pharmacotherapeutic group: M01AH Coxibs.
Pharmacology: Pharmacodynamics: The mechanism of action of celecoxib is via inhibition of prostaglandin synthesis primarily by inhibition of cyclooxygenase 2 (COX-2). At therapeutic concentrations in humans, celecoxib does not inhibit cyclooxygenase 1 (COX-1). COX-2 is induced in response to inflammatory stimuli. This leads to the synthesis and accumulation of inflammatory prostanoids, in particular prostaglandin E2, causing inflammation, edema and pain. Celecoxib acts as an anti-inflammatory, analgesic, and antipyretic agent in animal models by blocking the production of inflammatory prostanoids via COX-2 inhibition. In animal colon tumor models, celecoxib reduced the incidence and multiplicity of tumors.
In vivo and ex vivo studies show that celecoxib has a very low affinity for the constitutively expressed cyclooxygenase 1 enzyme (COX-1). Consequently, at therapeutic doses, celecoxib has no effect on prostanoids synthesized by activation of COX-1 thereby not interfering with normal COX-1 related physiological processes in tissues, particularly stomach, intestine and platelets.
Pharmacokinetics: Celecoxib is absorbed from the gastrointestinal tract; peak plasma concentrations being achieved after about 3 hours. Protein binding is about 97%. Celecoxib is metabolized in the liver mainly by the cytochrome P450 isoenzyme CYP2C9; the three identified metabolites are inactive as inhibitors of COX-1 or COX-2 enzymes. It is eliminated mainly as metabolites in the feces and urine; less than 3% is recovered as unchanged drug. The effective terminal half-life is about 11 hours. Celecoxib is distributed into breast milk. The pharmacokinetics of celecoxib may vary in different ethnic groups; it has been stated that the area under the curve is elevated in patients of Afro-Caribbean origin, although any clinical significance is unclear.
