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Variability of serum indomethacin concentrations after oral and intravenous administration to preterm infants
Insights
Oral or intravenous indomethacin effectively closed the patent ductus arteriosus in preterm infants. However, serum concentrations varied significantly with oral dosing, showing no direct link to ductal closure in individual cases.
Area of Science:
- Neonatal pharmacology
- Pediatric cardiology
Background:
- Patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS) are common in preterm infants.
- Indomethacin is a standard treatment for PDA in neonates.
Purpose of the Study:
- To compare the efficacy and pharmacokinetics of oral versus intravenous indomethacin for PDA closure in preterm infants.
- To investigate the relationship between serum indomethacin concentrations and ductal closure.
Main Methods:
- An uncontrolled, non-randomized study involving 15 preterm infants with PDA and RDS.
- Indomethacin administered orally or intravenously at 0.2 mg/kg every 12 hours up to three doses.
- Serum indomethacin levels measured 12 hours post-dose.
- Ductal closure assessed by clinical and echocardiographic methods.
Main Results:
- Similar rates of ductal closure and transient closure were observed for both oral and intravenous routes.
- Significant variability in serum indomethacin concentrations, particularly after oral administration.
- Mean serum concentrations were comparable between oral and intravenous routes after each dose.
- No direct correlation found between individual serum indomethacin concentrations and therapeutic effect.
Conclusions:
- Both oral and intravenous indomethacin are effective in closing PDA in preterm infants.
- Oral indomethacin administration can achieve sustained drug exposure necessary for ductal closure, despite concentration variability.
- Further research may be needed to optimize oral dosing strategies and understand concentration-effect relationships.
Abstract:
Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin (0.2 mg/kg) at 12 h intervals up to three times, either orally or intravenously, in an uncontrolled, non-randomized study. Serum indomethacin concentrations were determined in blood samples taken 12 h after dosing. There was considerable variability in the serum indomethacin concentrations, especially after oral administration, although the mean concentrations after each of the three doses were similar after both oral and intravenous administration. The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration. There was, however, no relation between concentration and effect in individual patients. The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration.