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 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.
Friedman
C A
CA
Mississippi Baptist Centers, Jackson.
Temple
D M
DM
Wender
D F
DF
Parks
B R
BR
Rawson
J E
JE
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*
D007213:Indomethacin