Indomethacin and the preterm infant with a patent ductus arteriosus: relationship between plasma concentration and ductus closure.
The relationship of indomethacin pharmacokinetics to clinical and echocardiographic evidence of closure of the patient ductus arteriosus (PDA) is described in 9 preterm infants. PDA closures occurred in 4 infants when peak indomethacin plasma concentrations were 0.71-1.10 micrograms/ml, mean 0.93 +/- 0.16 microgram/ml. With partial or no PDA response to oral treatment, the peak concentrations were 0.20-0.69 microgram/ml, mean 0.57 +/- 0.08 microgram/ml, p less than 0.01. The left atrial size in the study infants correlated inversely with the indomethacin peak concentrations, r = 0.75. The plasma apparent terminal half-life correlated with postnatal age, r = 0.75. All patients with peak concentrations greater than 0.50 microgram/ml had transient oliguria. This study suggests that a minimum indomethacin concentration may be needed to promote PDA constriction.
D001424:Bacterial Infections / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004374:Ductus Arteriosus, Patent / Q000097:blood* / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood* / Q000188:drug therapy; D007700:Kinetics; D009846:Oliguria / Q000139:chemically induced
D007213:Indomethacin