title: Metabolism and disposition of indomethacin in preterm infants.
abstract: 38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 or 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along with acid-labile metabolites using HPLC. Fifty-eight percent of the infants demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorter elimination half-life, smaller area under the plasma concentration-time curves and increased plasma clearance were associated with demethylation. Postnatal age greater than 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.
authors.affiliation: Mississippi Baptist Centers, Jackson.
authors.forename: C A
authors.initials: CA
authors.lastname: Friedman
authors.forename: D M
authors.initials: DM
authors.lastname: Temple
authors.forename: D F
authors.initials: DF
authors.lastname: Wender
authors.forename: B R
authors.initials: BR
authors.lastname: Parks
authors.forename: J E
authors.initials: JE
authors.lastname: Rawson
mesh_terms: D001724:Birth Weight; D002851:Chromatography, High Pressure Liquid; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*
chemical_list: D007213:Indomethacin