250 INDOMETHACIN DISPOSITION IN PREMATURE INFANTS: BLEEDING DUE TO PLATELET DYSFUNCTION AFTER SINGLE DOSES OF INDOMETHACIN

Abstract

Indomethacin failed to produce permanent ductal closure in any of four premature infants with patent ductus arteriosus to whom the drug was given (0.15-0.30 mg/kg). Indomethacin half-lives measured in two premature infants were 21 and 24 hours, much longer than in full-term newborns or adults. Platelet function, as measured by platelet aggregation, was grossly abnormal for two to four days after indomethacin administration, normal values returning only by the ninth and tenth day. Gastrointestinal bleeding and transient renal dysfunction occurred in one infant. Measurement of plasma indomethacin concentrations in sick, low birthweight infants could help to monitor indomethacin dose and dosage interval, thereby preventing drug accumulation and reducing toxicity. Further studies of potential toxicity seem to be indicated before instituting widespread indomethacin administration for ductal closure in premature infants.