Disposition of indomethacin in preterm infants

Indomethacin is currently used for the pharmacologic closure of PDA in preterm infants with respiratory distress syndrome. However, the response to the drug has been variable and the disposition of the drug in preterm infants is not well understood. We studied the pharmacokinetics of indomethacin in nine preterm infants with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 weeks. Three different dose schedules (0.1, 0.25, 0.3 mg/kg/dose) were used. The plasma half-life of indomethacin ranged from 11 to 20 hours. Peak levels were achieved within four hours and ranged from 0.027 to 0.310 μg/ml. The half-life in infants <32 weeks' gestation was significantly prolonged compared to that in infants >32 weeks. Protein-binding studies with ¹⁴C indomethacin showed that 98% of indomethacin was protein bound. Absorption of orally administered indomethacin appears to be poor and incomplete. No immediate major complications could be correlated to indomethacin therapy in this study.