Variability of serum indomethacin concentrations after oral and intravenous administration to preterm infants.

Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin (0.2 mg/kg) at 12 h intervals up to three times, either orally or intravenously, in an uncontrolled, non-randomized study. Serum indomethacin concentrations were determined in blood samples taken 12 h after dosing. There was considerable variability in the serum indomethacin concentrations, especially after oral administration, although the mean concentrations after each of the three doses were similar after both oral and intravenous administration. The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration. There was, however, no relation between concentration and effect in individual patients. The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration.