Pharmacokinetics of rofecoxib in children with sickle cell hemoglobinopathy

J Pediatr Hematol Oncol. 2004 Oct;26(10):661-4.

Abstract

Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor approved for the treatment of pain and arthritis in adults. It is available as a suspension, but there are no published pediatric pharmacokinetic data. This study characterized the disposition of rofecoxib in children with sickle cell hemoglobinopathy in a single-oral-dose, intensive pharmacokinetic study. Eight subjects aged 3 to 14 years (mean 8.9 years, 5 boys and 3 girls) received a single oral dose of rofecoxib (1 mg/kg, maximum 50 mg) as a suspension. Blood samples were collected over 72 hours following drug administration and plasma was assayed for rofecoxib using high-performance liquid chromatography (HPLC). Pharmacokinetic parameters (peak concentration [Cmax], time to reach peak concentration [tmax], area under the curve [AUC], oral clearance [Cl/F], elimination half-life [t1/2]) were calculated using standard noncompartmental methods. The mean dose was 35.6 mg (range 15-50 mg). Cmax averaged 582 +/- 129 ng/mL, with a median tmax of 4.0 hours. Secondary peaks were observed in two subjects. Two subjects were discharged at 12 hours, preventing characterization of elimination. In the remaining six subjects, Cl/F averaged 1.34 +/- 0.32 mL/min/kg, with a t1/2 of 14.8 +/- 4.5 hours. No significant adverse events were observed. The disposition of rofecoxib in children appears to be similar to that in adults, with comparable values for Cmax, tmax, t1/2, and Cl/F.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / blood
  • Analgesics, Non-Narcotic / pharmacokinetics*
  • Analgesics, Non-Narcotic / therapeutic use
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / complications
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis / drug therapy
  • Arthritis / etiology
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / blood
  • Cyclooxygenase Inhibitors / pharmacokinetics*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Female
  • Half-Life
  • Humans
  • Intestinal Absorption
  • Lactones / administration & dosage
  • Lactones / blood
  • Lactones / pharmacokinetics*
  • Lactones / therapeutic use
  • Male
  • Metabolic Clearance Rate
  • Pain / drug therapy
  • Pain / etiology
  • Sulfones
  • Suspensions

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Lactones
  • Sulfones
  • Suspensions
  • rofecoxib