Sign Out
Pharmacology: Pharmacodynamics: CYBEC is a non-steroidal anti-inflammatory drug (NSAIDs) reported to be a selective inhibitor of cyclooxygenase-2 (COX-2).
200 mg: The mechanism of action of Celecoxib is on prostaglandin synthesis by inhibiting COX-2. At therapeutic dose, Celecoxib does not inhibit cyclooxygenase-1 (COX-1). COX-1 is important for platelet aggregation, the regulation of blood flow in the kidney, the maintenance of the gastric mucosal barrier. Inhibition of COX-1 activity is considered a major contributor to NSAIDs GI toxicity.
400 mg: Celecoxib inhibits prostaglandin synthesis, via inhibition of cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors. Celecoxib has antipyretic, analgesic and anti-inflammatory properties. In studies using rodent models of colon cancer indicate that Celecoxib can decrease both the incidence and multiplicity of colon tumors.
Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations. Cyclooxygenase-1 (COX-1) is involved in platelet aggregation, maintenance of the gastric mucosal barrier and maintenance of renal perfusion.
COX-1 inhibition presumably is responsible for the unwanted effects on GI mucosa. Celecoxib's highly selective inhibition of cyclooxygenase-2 (COX-2) potentially may be associated with decreased risk of certain adverse effects (e.g., on GI mucosa).
Pharmacokinetics: 200 mg: Celecoxib is well absorbed from the gastrointestinal tract and peak plasma concentrations of the drug generally are attained within 3 hours after dosing in fasting individuals. Bioavailability was increased 10-20% and time to reach peak plasma concentrations of Celecoxib was delayed by 1-2 hours when Celecoxib capsules were administered with high fat meal. Celecoxib is about 97% bound to plasma proteins. The elimination half-life of Celecoxib is about 11 hours. Celecoxib is metabolized in the liver to inactive metabolites principally by the cytochrome P450 CYP2C9. Celecoxib is excreted in urine and feces principally as metabolites; less than 3% of the dose is excreted unchanged.
400 mg: Absorption: Celecoxib is well absorbed from the gastrointestinal tract and peak plasma concentrations of the drug generally are attained within 2-3 hours after dosing in fasting individuals. Oral bioavailability is about 99%. Bioavailability (AUC) was increased about 20% and resulting in a time to reach peak plasma concentrations of Celecoxib was about 4 hours when Celecoxib capsules were administered with high fat meal.
Distribution: The apparent volume of distribution of Celecoxib at steady state is about 400 L. Celecoxib is about 97% bound to plasma proteins, principally albumin and to a lesser extent, α1-acid glycoprotein. Celecoxib is not preferentially bound to erythrocytes in blood.
Metabolism: Celecoxib is metabolized in the liver mainly by the cytochrome P450 isoenzyme 2C9 which shows genetic polymorphism. Three identified metabolites; a primary alcohol, corresponding carboxylic acid and its glucuronide conjugate, are inactive as inhibitors of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2) enzymes.
In patients with poor metabolizer of the CYP2C9 isoenzyme, the metabolic clearance of Celecoxib may be decreased and plasma concentrations may be increased.
Excretion: Celecoxib is excreted in urine and feces principally as metabolites; less than 3% of the dose is excreted unchanged. Approximately 27% and 57% of the dose was excreted in the urine and feces, respectively. The principal metabolite in both urine and feces was the carboxylic acid metabolite (73% of the dose); small amounts of the glucuronide metabolites was present in urine. The plasma elimination half-life of Celecoxib is about 11 hours, and the apparent plasma clearance of the drug is about 500 mL/minute. The half-life of Celecoxib is prolonged in patients with renal or hepatic impairment and has been reported to be 13.1 hours in patients with chronic renal insufficiency and 11 to 13.1 hours in patients with mild or moderate hepatic impairment, respectively.
