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Metabolism and disposition of indomethacin in preterm infants

C A Friedman1, D M Temple, D F Wender

  • 1Mississippi Baptist Centers, Jackson.

Developmental Pharmacology and Therapeutics
|January 1, 1991
PubMed

Insights

Indomethacin metabolism in preterm infants with patent ductus arteriosus varies. Demethylation and older postnatal age are linked to treatment failure, impacting ductal closure.

Area of Science:

  • Neonatal Pharmacology
  • Pharmacokinetics
  • Drug Metabolism

Background:

  • Patent ductus arteriosus (PDA) is common in preterm infants.
  • Indomethacin is a standard treatment for PDA.
  • Understanding indomethacin's pharmacokinetics and metabolism is crucial for optimizing treatment efficacy.

Purpose of the Study:

  • To investigate the metabolism and pharmacokinetics of indomethacin in preterm infants with symptomatic PDA.
  • To identify factors influencing indomethacin's efficacy in closing the ductus arteriosus.

Main Methods:

  • 38 preterm infants with symptomatic PDA received intravenous indomethacin.
  • Plasma and urine samples were collected at various time points post-dose.
  • High-performance liquid chromatography (HPLC) was used to quantify indomethacin, its metabolites (demethylindomethacin, p-chlorobenzoic acid), and conjugates.

Main Results:

  • 58% of infants demethylated indomethacin.
  • Half of the unchanged and demethylated drug was excreted as conjugates in urine.
  • 14% of infants 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 > 2 weeks correlated with demethylation and treatment failure.

Conclusions:

  • Indomethacin metabolism, including demethylation and deacylation, occurs in preterm infants.
  • Demethylation and older postnatal age are associated with impaired indomethacin efficacy for PDA closure.
  • These findings highlight the importance of considering individual drug metabolism and patient age in indomethacin therapy for PDA.

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