Objective: The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days.
Methods: Medical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL.
Results: Of the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14).
Conclusion: The current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.