Icox Mechanism of Action

Pharmacology: Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic drugs, [NSAIDs], Coxibs, Selective Cox-2 Inhibitor. ATC code: M01AH01.
Pharmacodynamics: Mechanism of action: Celecoxib is an oral, selective, cyclooxygenase-2 (COX-2) inhibitor within the dose range (200-400 mg daily). No statistically significant inhibition of COX-1 was observed in this dose range.
Pharmacodynamic effects: Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2, have been identified, COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function). It may also play a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in human but its relevance to ulcer healing has not been established.
The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of significance in patients at risk of thrombo-embolic reactions. COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e.g. thiazides, furosemide) but differs from arylamine sulfonamides (e.g. sulfamethoxazole and other sulfonamide antibiotics).
Pharmacokinetics: Absorption: Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours. Dosing with food (high fat meal) delays absorption of celecoxib by about 1 hour resulting in a T_max of about 4 hours and increases bioavailability by about 20%.
Distribution: Plasma protein binding is about 97% at therapeutic plasma concentrations and the drug is not preferentially bound to erythrocytes.
Biotransformation: Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma i.e., a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate. Cytochrome P450 2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism.
Elimination: Celecoxib is mainly eliminated by metabolism. Less than 1% of the dose is excreted unchanged in urine. The inter-subject variability in the exposure of celecoxib is about 10-fold, Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic, dose range. Elimination half-life is 8-12 hours. Steady state plasma concentrations are reached within 5 days of treatment.