COXIGET Capsule Ref.[115702] Active ingredients: Celecoxib

Absorption

Peak plasma levels of celecoxib occur approximately 3 hours after an oral dose. Under fasting conditions, both peak plasma levels (C_max) and area under the curve (AUC) are roughly dose proportional up to 200 mg b.i.d.; at higher doses there are less than proportional increases in C_max and AUC. With multiple dosing, steady state conditions are reached on or before day 5.

Effect of food and antacid

When celecoxib was taken with a high fat meal, peak plasma levels were delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Under fasting conditions, at doses above 200 mg, there is less than a proportional increase in C_max and AUC, which is thought to be due to the low solubility of the drug in aqueous media. Co-administration of celecoxib with an aluminum and magnesium containing antacid resulted in a reduction in plasma celecoxib concentrations with a decrease of 37% in C_max and 10% in AUC. Celecoxib, at doses up to 200 mg b.i.d. can be administered without regard to timing of meals. Higher doses (400 mg b.i.d.) should be administered with food to improve absorption.

Distribution

In healthy subjects, celecoxib is highly protein bound (~97%) within the clinical dose range. The apparent volume of distribution at steady state (V_ss/F) is approximately 400L, suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red blood cells

Metabolism

Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.

Excretion

Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces. The primary metabolite in both urine and feces was the carboxylic acid metabolite (73% of dose) with low amounts of the glucuronide also appearing in the urine. The effective half-life is approximately 11 hours under fasting conditions. The apparent plasma clearance (CL/F) is about 500mL/min.

Special populations

Geriatric

At steady state, elderly subjects (over 65 years old) had a 40% higher C_max and a 50% higher AUC compared to the young subjects. In elderly females, celecoxib C_max and AUC are higher than those for elderly males, but these increases are predominantly due to lower body weight in elderly females. Dose adjustment in the elderly is not generally necessary. However, for patients of less than 50kg in body weight, initiate therapy at the lowest recommended dose.

Pediatric

Celecoxib has not been investigated in JRA pediatric patients below 2 years of age, in patients with body weight less than 10kg or beyond 24 weeks.

Hepatic impairment

Steady state celecoxib AUC is increased about 40% and 180% in subjects with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment respectively, as compared to healthy control subjects. Therefore, the daily-recommended dose of celecoxib should be reduced by approximately 50% in patients with moderate (Child-Pugh Class B) hepatic impairment. Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied.

Renal impairment

Studies indicate that celecoxib AUC was approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60mL/min) than that seen in subjects with normal renal function. No significant relationship was found between GFR and celecoxib clearance. Patients with severe renal insufficiency have not been studied.