Pharmacology: Celecoxib exhibits anti-inflammatory, analgesic, and antipyretic activities by selectively inhibiting cyclooxygenase-2 (COX-2) isoenzymes resulting in inhibition of prostaglandin synthesis. Traditional non-steroidal anti-inflammatory drugs (NSAIDs) appear to inhibit prostaglandin synthesis through inhibition of both COX-1 and COX-2 isoenzymes.
At therapeutic doses, celecoxib does not inhibit COX-1 isoenzyme, thus, it does not interfere with the normal COX-1 related physiological processes in tissues, such as the stomach, intestine and platelets.
Pharmacokinetics: Bioavailability: Celecoxib is well absorbed from the GI tract. Peak plasma levels occur approximately 2 to 3 hours after the drug is given orally under fasting conditions. After oral administration of a single 200 mg dose of celecoxib in healthy fasting adults, peak plasma concentrations (Cmax) of the drug averaged 705 ng/mL. When celecoxib was taken with a high fat meal (24 g fat), bioavailability (AUC) was increased by 10 to 20% and time to reach peak plasma levels (tmax) was delayed by 1 to 2 hours compared with administration with a medium-fat meal (8 g fat) or under fasting conditions. The AUC and plasma concentration 12 hours after a celecoxib dose were slightly higher when the drug was given in the evening versus in the morning. Under fasting conditions, at doses above 200 mg, there is less than a proportional increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media. After oral administration of celecoxib at recommended doses of 200 to 400 mg/day, steady-state plasma concentrations are reached within five days. Celecoxib doses up to 200 mg twice a day can be administered without regard to timing of meals. Higher doses (400 mg twice a day) should be given with food to improve absorption. Celecoxib's protein binding is 97%. The apparent volume of distribution at steady state is about 400 L (about 7.14 L/kg), suggestive of extensive tissue distribution. Celecoxib is not bound to erythrocytes. It is not known whether celecoxib crosses human placenta.
Celecoxib is extensively metabolized in the liver; metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites have been identified in human plasma: a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate.
Celecoxib's metabolites do not have pharmacologic activity as COX-1 and 2 inhibitors. (See Interactions).
Celecoxib is excreted in urine and feces principally as metabolites; less than 3% of the dose is excreted unchanged. Under fasted condition, the effective half-life is approximately 11 hours. The apparent plasma clearance (CL/F) is about 500 mL/min.