A comparison of oral and intravenous indomethacin dispositions in the premature infant with patent ductus arteriosus.

Plasma concentrations of indomethacin were studied in 18 premature infants exhibiting significant patent ductus arteriosus (sPDA) after either intravenous or oral drug administration. Oral absorption of indomethacin was prolonged and bioavailability, based on area under the curve (AUC), was less than 20%. The mean volume of distribution for indomethacin was 0.36 l/kg and showed only a small variation between subjects. The drug elimination half-life ranged from 10-25 hours and demonstrated a significant correlation with gestational age. There was no evidence to support dose-dependent clearance or enterohepatic circulation in this study. Side effects of indomethacin were limited in one infant. No significant changes were observed in hematocrit, platelet count, and serum creatinine. The results from this study support the continued use of intravenous sodium indomethacin trihydrate at doses of 0.2 mg/kg and intervals of 18-24 hours for pharmacological treatment of sPDA.