Single-dose and steady-state pharmacokinetics of celecoxib in children.

Background And Objective: Celecoxib is a member of a novel group of agents that selectively inhibit cyclooxygenase 2 (COX-2). COX-2 inhibitors have emerged as an important class of drugs because of the lower incidence of side effects when compared with traditional nonsteroidal anti-inflammatory drugs, which inhibit both cyclooxygenase 1 and COX-2. Because children often differ from adults with respect to drug disposition, the objective of this study was to determine the single-dose and steady-state pharmacokinetics of celecoxib in pediatric patients.

Methods: Celecoxib plasma concentrations were determined at intervals over 12 hours after a 250-mg/m(2) dose and again 1 week later after twice-daily dosing (steady state).

Results: Peak plasma concentrations (1234 +/- 528 microg/L) were achieved 3 hours after drug administration. The area under the celecoxib plasma concentration-time curve was 7709 +/- 3176 microg/L x h, the elimination half-life (t(1/2)) was 3.7 +/- 1.1 hours, the apparent volume of distribution was 7.9 +/- 7.8 L/kg, and the lower oral clearance of the drug was 1.4 +/- 1.0 L x h(-1) x kg(-1). Statistical analysis revealed a significantly lower [corrected] apparent oral clearance and longer t(1/2) (P <.05) at steady state compared with pharmacokinetics after a single dose. In addition, when the results were compared in children and adults, the drug was cleared approximately twice as fast in children and had a t(1/2) that was approximately half as long.

Conclusions: This is the first report of celecoxib pharmacokinetics in children, and the results indicate that there are significant differences between children and adults with respect to celecoxib disposition; hence these data may have implications when dosing schedules are planned for this population.