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Pharmacokinetics of postoperative intravenous indomethacin in children
K T Olkkola1, E L Maunuksela, R Korpela
1Department of Clinical Pharmacology, University of Helsinki, Finland.
Insights
Pediatric patients aged one to four years showed early maturation of indomethacin pharmacokinetics. By one year of age, children exhibit mature indomethacin disposition, similar to adults.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Metabolism
Background:
- Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used for various pediatric conditions.
- Understanding the pharmacokinetic profile of indomethacin in children is crucial for appropriate dosing and therapeutic efficacy.
- Previous studies suggest potential differences in drug disposition between pediatric age groups and adults.
Purpose of the Study:
- To investigate the pharmacokinetic disposition of indomethacin in children aged one to four years.
- To determine key pharmacokinetic parameters, including half-life, volume of distribution, and clearance.
- To assess the developmental maturation of indomethacin pharmacokinetics in early childhood.
Main Methods:
- Intravenous administration of indomethacin (0.35 mg/kg) over 15 minutes to pediatric subjects.
- Serial blood sample collection for up to 24 hours post-infusion.
- Quantification of serum indomethacin concentrations using gas chromatography.
- Non-linear regression analysis to fit data to a two-compartment open mammillary model.
Main Results:
- Calculated pharmacokinetic parameters included alpha half-life (25.2 ± 11.3 min), beta half-life (366 ± 295 min), steady-state volume of distribution (0.74 ± 0.75 L/kg), volume during elimination phase (1.53 ± 1.27 L/kg), and total body clearance (3.2 ± 1.7 mL/min/kg).
- The pharmacokinetic profile suggests rapid elimination and distribution consistent with mature metabolic pathways.
- Individual data analysis revealed variability but overall trends indicated early maturation.
Conclusions:
- Children aged one to four years demonstrate pharmacokinetic parameters for indomethacin that suggest early maturation.
- Indomethacin disposition appears to be mature by one year of age in children.
- These findings have implications for optimizing indomethacin therapy in pediatric populations.
Abstract:
The disposition of indomethacin was studied in children aged one to four years. Indomethacin 0.35 mg/kg was administered as an intravenous infusion during 15 min. Venous blood samples were collected until 24 hr after infusion. Serum indomethacin was determined with gas chromatography. Using a non-linear regression analysis, the individual data were fitted by a two-compartment open mammillary model with central elimination. Calculated pharmacokinetic parameters were (mean +/- SD); alpha half-life 25.2 +/- 11.3 min; beta half-life 366 +/- 295 min; steady-state volume of distribution 0.74 +/- 0.75 l/kg; volume during elimination phase 1.53 +/- 1.27 l/kg; total body clearance 3.2 +/- 1.7 ml/min./kg. Accordingly, with respect to the pharmacokinetics of indomethacin, children seem to mature early, not later than at the age of one year.