Pharmacology: Pharmacodynamics: Celecoxib inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors, has antipyretic, analgesic, and anti-inflammatory properties. Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.
Pharmacokinetics: Absorption: Prolonged due to low solubility.
Distribution: Vd (apparent): Children and Adolescents ~7-16 years (steady-state): 8.3 ± 5.8 L/kg.
Adults: ~ 400 L.
Protein binding: ~97% primarily to albumin: binds to alpha1-acid glycoprotein to a lesser extent.
Metabolism: Hepatic via CYP2C9, form inactive metabolites (a primary alcohol, corresponding carboxylic acid, and its glucuronide conjugate).
Bioavailability: Absolute: Unkonown.
Half-life elimination: Children and Adolescents ~ 7-16 years (steady-state): 6 ± 2.7 hours (range: 3-10 hours); Adults: ~11 hours (fasted).
Time to peak: Children: Median: 3 hours (range: 1-5.8 hours); Adults: ~3 hours.
Excretion: Feces (~57% as metabolites, <3% as unchanged drug).
Urine (~27% as metabolites, <3% as unchanged drug).
Primary metabolites in feces and urine: Carboxylic acid metabolite (73% of dose); low amounts of glucuronide metabolite appear in urine.