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Pharmacokinetics of phenytoin in children with acute neurotrauma

N B O'Mara1, P R Jones, D L Anglin

  • 1College of Pharmacy, Ohio State University, Columbus 43210, USA.

Critical Care Medicine
|August 1, 1995
PubMed

Insights

Critically ill children with acute neurologic injury receiving intravenous phenytoin may need higher doses than typically predicted. Dosing adjustments are crucial for achieving therapeutic phenytoin concentrations in pediatric patients.

Area of Science:

  • Pharmacology
  • Pediatric Critical Care
  • Neurology

Background:

  • Intravenous phenytoin is used to manage seizures in critically ill children.
  • Understanding phenytoin pharmacokinetics is essential for optimizing therapeutic outcomes in pediatric patients with acute neurologic injury.

Purpose of the Study:

  • To determine the pharmacokinetics of intravenous phenytoin in critically ill infants and children with acute neurologic injury.
  • To establish appropriate dosing strategies for phenytoin in this vulnerable population.

Main Methods:

  • Prospective, descriptive study conducted in a pediatric intensive care unit.
  • Involved 16 children (0.5-16 years) with acute neurologic injuries receiving intravenous phenytoin.
  • Measured total and free phenytoin concentrations, and urinary metabolite excretion.

Main Results:

  • Observed lower-than-predicted Michaelis-Menten constant (Km) and higher-than-predicted maximum rate of metabolism (Vmax) in survivors.
  • Free phenytoin fractions showed significant inter-patient variability.
  • Wide variability in the ratio of phenytoin to its metabolite excreted in urine.

Conclusions:

  • Children aged 0.5-9 years with neurologic injury may require 8-10 mg/kg/day of phenytoin.
  • Children aged 10-16 years may require 6-8 mg/kg/day to achieve therapeutic concentrations.
  • These findings suggest adjusted dosing is necessary for effective phenytoin therapy in pediatric neurologic patients.
Abstract

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