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Disposition of indomethacin in preterm infants
Insights
Indomethacin treatment for premature infants with respiratory distress syndrome shows variable responses. Half-life is longer in younger infants, and oral absorption appears poor, suggesting careful dosing is needed.
Area of Science:
- Neonatal pharmacokinetics
- Pharmacologic closure of patent ductus arteriosus (PDA)
Background:
- Indomethacin is used to close PDA in preterm infants with respiratory distress syndrome (RDS).
- Drug response and disposition in preterm infants are not well understood.
- Variability in indomethacin efficacy necessitates further pharmacokinetic investigation.
Purpose of the Study:
- To investigate the pharmacokinetics of indomethacin in preterm infants.
- To evaluate the impact of gestational age on indomethacin disposition.
- To assess the absorption and protein binding of indomethacin in this population.
Main Methods:
- Studied nine preterm infants (birth weight 800–1,960 gm, gestational age 28–36 weeks).
- Administered three dose schedules (0.1, 0.25, 0.3 mg/kg).
- Measured plasma half-life, peak levels, and protein binding (using 14C indomethacin).
Main Results:
- Plasma half-life ranged from 11 to 20 hours.
- Peak indomethacin levels (0.027–0.310 µg/ml) were achieved within 4 hours.
- Significantly prolonged half-life observed in infants < 32 weeks gestation compared to those > 32 weeks.
- 98% of indomethacin was protein bound.
- Oral absorption appeared poor and incomplete.
Conclusions:
- Gestational age significantly influences indomethacin half-life in preterm infants.
- Poor oral absorption and prolonged half-life in younger infants may explain variable responses.
- Further research into optimal dosing strategies for indomethacin in preterm neonates is warranted.
Abstract:
Indomethacin is currently used for the pharmacologic closure of PDA in preterm infants with respiratory distress syndrome. However, the response to the drug has been variable and the disposition of the drug in preterm infants is not well understood. We studied the pharmacokinetics of indomethacin in nine preterm infants with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 weeks. Three different dose schedules (0.1, 0.25, 0.3 mg/kg dose) were used. The plasma half-life of indomethacin ranged from 11 to 20 hours. Peak levels were achieved within four hours and ranged from 0.027 to 0.310 microgram/ml. The half-life in infants less than 32 weeks' gestation was significantly prolonged compared to that in infants greater than 32 weeks. Protein-binding studies with 14C indomethacin showed that 98% of indomethacin was protein bound. Absorption of orally administered indomethacin appears to be poor and incomplete. No immediate major complications could be correlated to indomethacin therapy in this study.