Serum indomethacin concentrations after intravenous administration to preterm infants with patent ductus arteriosus

Abstract

Six preterm infants with PDA received 14 treatments with indomethacin 0.2 mg/kg intravenously. Auscultatory and echocardiographic assessment indicated closure of the duct in 2, partial closure in 2, and no effect in 2 infants. The mean serum concentration of indomethacin was: 15 min after the first injection 1 314 ng/ml, after 1 hour 970 ng/ml, after 6 hours 718 ng/ml, and after 24 hours 388 ng/ml. The mean half-life of indomethacin in the serum was 20 hours (range 9-50 hours). Side effects in all infants were hyponatraemia, decreased urinary output, decreased urinary sodium excretion, and weight gain. One infant had transient thrombocytopenia and gastrointestinal haemorrhage. By intravenous administration of indomethacin in a dose of 0.2 mg/kg to preterm infants a sufficiently high serum concentration is obtained shortly after the injection. To maintain a high serum concentration for a longer period it is recommended to give a second dose of 0.2 mg/kg after 6 hours and if necessary a third dose of 0.1 mg/kg 24 hours after the first dose.