Phenobarbital and phenytoin in neonatal seizures: metabolism and tissue distribution

Area of Science:

• Neonatal pharmacology
• Neuroscience
• Pediatric neurology

Background:

• Neonatal seizures require prompt and effective anticonvulsant therapy.
• Phenobarbital and phenytoin are commonly used anticonvulsants in newborns.
• Understanding drug distribution in the neonatal brain is crucial for optimizing treatment.

Purpose of the Study:

• To determine the appropriate loading and maintenance doses of phenobarbital and phenytoin for newborns.
• To investigate the oral bioavailability of phenytoin in neonates.
• To compare the brain:plasma distribution of phenobarbital and phenytoin in newborns.

Main Methods:

• Intravenous administration of phenobarbital and phenytoin loading doses (15-20 mg/kg).
• Intravenous administration of maintenance doses (3-4 mg/kg).
• Measurement of plasma anticonvulsant levels and brain:plasma ratios.

Main Results:

• Loading doses of 15-20 mg/kg of phenobarbital and phenytoin achieve therapeutic levels.
• Maintenance doses of 3-4 mg/kg maintain therapeutic levels.
• Phenytoin shows unpredictable oral absorption.
• Phenobarbital and phenytoin brain:plasma ratios were 0.71 and 1.28 respectively.
• Phenobarbital's brain:plasma ratio increased with gestational age.
• Phenytoin concentrated in gray matter; phenobarbital distributed equally in gray and white matter.

Conclusions:

• Specific intravenous loading and maintenance doses for phenobarbital and phenytoin are established for neonates.
• Phenytoin's oral route is unreliable in newborns.
• Differential brain region distribution of these anticonvulsants is observed in neonates.