Fosphenytoin pharmacokinetics remain unpredictable, especially when the drug is used in critically ill patients with fluctuating factors affecting drug levels and often necessitating dose adjustments.

Current methods of calculating a reloading dose in patients with subtherapeutic free phenytoin concentration levels do not consistently result in therapeutic free concentrations on subsequent days.

A modified calculation with less emphasis on volume of distribution was associated with a twofold increased chance of attaining a therapeutic free phenytoin level on the subsequent day.