METABOLISM AND DISPOSITION OF INDOMETHACIN IN PRETERM INFANTS

38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 o r 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along wi th acid-labile metabolites using HPLC. Fifty-eight percent of the infa nts demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorte r elimination half-life, smaller area under the plasma concentration-t ime curves and increased plasma clearance were associated with demethy lation. Postnatal age > 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.