Starcox Mechanism of Action

Pharmacology: Cyclooxygenase (COX) is an enzyme that is responsible for the formation of prostanoids. The three main groups of prostanoids - prostaglandins, prostacyclins, and thromboxanes - each involved in the inflammatory response. There are two, if not three, known types of cyclooxygenase (COX-1, COX-2, and COX-3).
COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, an enzyme involved in the inflammation pathway, while sparing COX-1, thereby reducing gastrointestinal toxicity.
Etoricoxib is a selective COX-2 inhibitor. It selectively inhibits isoform 2 of cyclooxygenase enzyme (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted. COX-2 selective inhibitor (aka "COXIB") showed less marked activity on type 1 cyclooxygenase compared to traditional non-steroidal anti-inflammatory drugs (NSAID).
Pharmacokinetics: Absorption: Orally administered etoricoxib is well absorbed. The mean oral bioavailability is approximately 100%. Following 120 mg-once-daily dosing to steady state, the peak plasma concentration (geometric mean Cmax = 3.6 mcg/mL) was observed at approximately 1 hour (Tmax) after administration to fasted adults. The geometric mean AUC0-24 hrs was 37.8 mcg hr/mL. The pharmacokinetics of etoricoxib in 12 healthy subjects were similar (comparable AUC, Cmax within approximately 20%) when administered alone, with a magnesium/aluminum hydroxide antacid, or a calcium carbonate antacid (approximately 50 mEq acid-neutralizing capacity).
Distribution: Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 0.05 to 5 mcg/mL. The volume of distribution at steady state (Vdss) is approximately 120 L in humans.
Metabolism: Etoricoxib is extensively metabolized with <1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6-hydroxymethyl derivative. These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors. None of these metabolites inhibit COX-1.
Elimination: Following administration of a single 25 mg radiolabeled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in feces, mostly as metabolites. Less than 2% was recovered as unchanged drug.
Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion. Steady state concentrations of etoricoxib are reached within seven days of once-daily administration of 120 mg, with an accumulation half-life of approximately 2, corresponding to an accumulation half-life of approximately 22 hours. The plasma clearance is estimated to be approximately 50 mL/min.