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Indomethacin and the preterm infant with a patent ductus arteriosus: relationship between plasma concentration and
Insights
Effective closure of the patent ductus arteriosus (PDA) in preterm infants requires a minimum indomethacin concentration. Higher indomethacin levels correlate with PDA closure and reduced left atrial size, but may cause transient oliguria.
Area of Science:
- Neonatal Pharmacology
- Pediatric Cardiology
Background:
- Patent ductus arteriosus (PDA) is a common complication in preterm infants.
- Indomethacin is a frequently used medication to close PDA.
Purpose of the Study:
- To investigate the relationship between indomethacin pharmacokinetics and PDA closure in preterm infants.
- To determine optimal indomethacin concentrations for PDA treatment.
Main Methods:
- Studied 9 preterm infants receiving oral indomethacin.
- Monitored indomethacin plasma concentrations, clinical and echocardiographic PDA evidence.
- Analyzed correlations between drug levels, PDA closure, left atrial size, and postnatal age.
Main Results:
- PDA closure occurred at peak indomethacin concentrations of 0.71-1.10 µg/ml (mean 0.93 µg/ml).
- Lower concentrations (0.20-0.69 µg/ml) showed partial or no PDA response.
- Inverse correlation (r=0.75) between peak indomethacin and left atrial size.
- Transient oliguria observed in infants with peak concentrations >0.50 µg/ml.
Conclusions:
- A minimum indomethacin plasma concentration appears necessary for effective PDA constriction.
- Indomethacin pharmacokinetics influence treatment outcomes and potential side effects in preterm neonates.
Abstract:
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.