Related Experiment Videos
Fosphenytoin in infants
M Takeoka1, K S Krishnamoorthy, T B Soman
1Department of Neurology, Massachusetts General Hospital, Boston 02114, USA.
Insights
Fosphenytoin, a safer alternative to phenytoin for treating seizures, presented challenges in achieving therapeutic serum levels in infants. Dosing adjustments were often insufficient to maintain target phenytoin concentrations in this pediatric population.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Pharmacokinetics
Background:
- Phenytoin has a high pH (11), increasing risks of cardiovascular and cutaneous side effects.
- Fosphenytoin, a prodrug of phenytoin, offers a near-neutral pH (8.6), enhancing safety and administration options (IV/IM).
- Fosphenytoin is converted 1:1 to phenytoin (mg PE:mg), simplifying dose calculations.
Abstract:
In comparison with phenytoin preparations, which have a pH value of 11, fosphenytoin, a phosphorylated prodrug of phenytoin, has a pH value of only 8.6, which decreases the risk of cardiovascular and cutaneous side effects. The near-neutral pH value of fosphenytoin allows effective intravenous or intramuscular administration. A 1-mg phenytoin equivalent (PE) of fosphenytoin is converted to 1 mg of phenytoin in adults. We describe four infants whose seizures were treated with intravenous fosphenytoin. We had difficulty maintaining therapeutic serum phenytoin levels of 10 to 20 microg/mL on doses of 5 to 8 mgPE/kg/day, and many bolus doses of 5 to 10 mgPE/kg or maintenance doses of more than 10 mgPE/kg/day were given. Despite increased doses in three out of the four patients, a therapeutic serum phenytoin level was not maintained. From our experience, careful and individual dosing of fosphenytoin in this age group can be considered.