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Phenytoin (PHT) elimination half-life (t50%) in infants varies significantly with age and concentration. PHT levels may decrease with constant doses due to these factors in newborns.
Area of Science:
- Pharmacokinetics
- Neonatal Medicine
- Clinical Pharmacology
Background:
- Phenytoin (PHT) is commonly used to treat seizures in infants.
- Understanding PHT elimination is crucial for optimizing therapeutic drug monitoring in neonates.
Purpose of the Study:
- To determine the apparent half-life (t50%) of phenytoin (PHT) in a cohort of infants.
- To investigate the influence of postnatal age and initial PHT concentration (Ci) on PHT elimination.
Main Methods:
- Measured PHT apparent half-life (t50%) 30 times in 16 infants (2-36 days old) with seizures.
- Analyzed the relationship between t50%, postnatal age, and initial PHT concentration (Ci).
Main Results:
- During the first week of life, PHT t50% ranged widely from 6 to 140 hours.
- After the first week, PHT elimination became concentration-dependent, with t50% decreasing as postnatal age increased.
- Controlling for Ci, average t50% decreased threefold from the first week (57.3 ± 48.2 hours) to the fourth week (19.7 ± 1.31 hours).
Conclusions:
- Both age-related changes and concentration-dependent PHT elimination contribute to decreasing PHT levels in newborns receiving constant doses.
- These findings highlight the importance of individualized dosing and therapeutic drug monitoring for phenytoin in the neonatal population.
Abstract:
We measured the apparent half-life (t50%) of phenytoin (PHT) 30 times in 16 infants (aged 2 to 36 days) who had seizures. During the first week of life, the t50%s ranged from 6 to 140 hours. After the first week, the concentration dependence of PHT elimination was demonstrated; the t50% was related to the initial concentration (Ci). The t50% also decreased with postnatal age. Controlling for a Ci of 18 mg per liter, the average t50% decreased threefold between the first (57.3 +/- 48.2 hours) and fourth weeks (19.7 +/- 1.31). In newborns, both age-related changes and the concentration dependence of PHT elimination can cause PHT levels to decrease when constant doses are given.