Etoricoxib Auxilto Mechanism of Action

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids, coxibs. ATC code: M01AH05.
Pharmacology: Pharmacodynamics: Mechanism of Action: Etoricoxib is an oral, selective cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range. Etoricoxib produces dose-dependent inhibition of COX-2 without inhibition of COX-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric prostaglandin synthesis and had no effect on platelet function.
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 man, but its relevance to ulcer healing has not been established.
Pharmacokinetics: Absorption: Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 100%. Peak plasma concentrations occur in about 1 hour in fasted adults; food delays absorption by about 2 hours, although it has no effect on the extent of absorption.
Distribution: Etoricoxib is approximately 92% bound to human plasma. The volume of distribution at steady state (Vdss) was approximately 120 L in humans. Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.
Metabolism: Etoricoxib is extensively metabolised with <1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6'-hydroxymethyl derivative is catalysed by CYP enzymes. Five metabolites have been identified in man. The principal metabolite is the 6'-carboxylic acid derivative of etoricoxib formed by further oxidation of 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 inhibits COX-1.
Elimination: Etoricoxib is excreted mainly via the urine (70%) and with only 20% of a dose appearing in the faeces. At steady state, the half-life is approximately 22 hours.
Characteristics in patients: Elderly patients: Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young.
Gender: The pharmacokinetics of etoricoxib are similar between men and women.
Hepatic impairment: Patients with mild hepatic dysfunction (Child-Pugh score 5-6) administered etoricoxib 60 mg once daily had a higher mean AUC as compared to healthy subjects given the same regimen. Patients with moderate hepatic dysfunction (Child-Pugh score 7-9) administered etoricoxib 60 mg every other day had similar mean AUC to the healthy subjects given etoricoxib 60 mg once daily; etoricoxib 30 mg once daily has not been studied in this population. There is no clinical or pharmacokinetic data in patients with severe hepatic dysfunction (Child-Pugh score ≥10).
Renal impairment: The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with moderate to severe renal insufficiency and patients with end-stage renal disease on haemodialysis were not significantly different from those in healthy subjects. Haemodialysis contributed negligibly to elimination (dialysis clearance approximately 50 mL/min).
Paediatric patients: The pharmacokinetics of etoricoxib in paediatric patients (<12 years old) have not been studied.
The pharmacokinetics in adolescents (aged 12 to 17) weighing 40 to 60 kg given etoricoxib 60 mg once daily and adolescents >60 kg given etoricoxib 90 mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90 mg once daily. Safety and effectiveness of etoricoxib in paediatric patients have not been established.