Pharmacokinetics of Rofecoxib in Children With Sickle Cell Hemoglobinopathy

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 [t½]) 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 t½ 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, t½, and Cl/F.