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Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
09:04

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods

Published on: September 10, 2018

Plasma and cerebrospinal fluid concentrations of indomethacin in children after intravenous administration

Anne Mannila1, Elina Kumpulainen, Marko Lehtonen

  • 1Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland.

Journal of Clinical Pharmacology
|December 29, 2006
PubMed

Insights

Indomethacin penetrates the cerebrospinal fluid (CSF) in children, potentially causing central nervous system (CNS) effects. This study measured indomethacin levels in CSF and plasma after intravenous infusion in pediatric patients.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Neuroscience

Background:

  • Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used for various pediatric conditions.
  • Understanding its penetration into the central nervous system (CNS) is crucial for assessing efficacy and safety in children.

Purpose of the Study:

  • To quantify the cerebrospinal fluid (CSF) permeation of indomethacin in healthy children.
  • To correlate CSF and plasma concentrations of indomethacin.
  • To identify potential CNS adverse effects related to indomethacin exposure.

Main Methods:

  • Intravenous infusion of indomethacin (0.35 mg/kg) in 31 children (4-144 months) undergoing surgery.
  • Collection of CSF and plasma samples post-infusion.
  • Quantification of indomethacin concentrations using validated analytical methods.

Main Results:

  • Indomethacin was detected in CSF, with concentrations ranging from 0.2 to 5.0 ng/mL (median 1.4 ng/mL).
  • The CSF to plasma concentration ratio was consistently low (<0.01).
  • Five out of 12 nonserious adverse events were CNS-related, including agitation.

Conclusions:

  • Indomethacin effectively permeates the CSF in pediatric patients.
  • The observed CNS effects suggest a direct impact of indomethacin within the CNS.
  • Further research is warranted to fully elucidate the clinical implications of indomethacin's CNS penetration in children.

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