title: Single-dose and steady-state pharmacokinetics of celecoxib in children.
abstract: 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.
authors.affiliation: New Agents and Innovative Therapy Program, Divisions of Hematology/Oncology and Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Stempak
authors.forename: Janet
authors.initials: J
authors.lastname: Gammon
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baruchel
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000068579:Celecoxib; D002648:Child; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib