Rationale: Fosphenytoin (FOS) is a water-soluble phenytoin (PHT) prodrug that can be given either intravenously (IV) or intramuscularly (IM). It is rapidly converted to PHT by tissue and blood phosphatases in pediatric and adult patients. While the IM route offers advantages in neonates because of the variable oral bioavailability of PHT and the problems with emergency IV access, IM FOS studies have been limited to infants >6 months. This report describes our experience with IM FOS administration in neonates.

Methods: Loading doses of IM FOS were given to 3 neonates requiring PHT for the treatment of seizures. Loading doses were calculated to increase plasma PHT concentrations to 10-15μg/mL. Loading doses were given as a single IM injection in the anterior lateral thigh. Heart and respiratory rates and oxygen saturations were continuously monitored. Injection sites were inspected for signs of inflammation for a minimum of 5 days. Plasma samples for analysis of total and free PHT concentrations by HPLC were obtained at 0, 1, 3 and between 6 and 12 hours post IM FOS.

Results: Gestational ages were 32-38 weeks, postnatal ages were 15-47 days and weights were 2551-3411 grams. Pharmacokinetic results are presented in the table below. No adverse effects such as bradycardias, desaturations and reactions at the injection sites were noted. Mean± SD FOS injection volumes were 0.7±0.2 mL.

Table 1 No caption available.
Full size table

Conclusion: This initial evaluation indicates that IM fosphenytoin provides a safe and well tolerated alternative for the rapid achievement of therapeutic phenytoin concentrations in neonates.

Cpredose = predose PHT concentration; Cmax-total = peak total PHT concentration; Tmax = time of peak PHT concentration; Vd = volume of distribution; fu = unbound fraction of PHT concentration; Cmax-free = peak free PHT concentration