Evaluation of phenytoin serum levels following a loading dose in the acute hospital setting

Purpose Due to the complex pharmacokinetic profiles of phenytoin (PHT) and fosphenytoin (FOS), achieving sustained, targeted serum PHT levels in the first day of use is challenging. Methods A population based approach was used to analyze total serum PHT (tPHT) level within 2–24 h of PHT/FOS loading with or without supplementary maintenance or additional loading doses among PHT-naïve patients in the acute hospital setting. Adequate tPHT serum level was defined as ≥20 μg/mL. Results Among 494 patients with 545 tPHT serum levels obtained in the first 2–24 h after the loading dose (LD), tPHT serum levels of either <or ≥ 20 μg/mL were observed along wide and overlapping cumulative dose ranges. Among those receiving 15–20 mg/kg and 20–55 mg/kg weight-based loading dose, 63% and 51% respectively did not attain tPHT serum level of ≥20 μg/mL even within the first 6 h of treatment. For the 393 available concomitant free and total serum PHT levels, correlation was weak, r = 0.36. Conclusion Close laboratory surveillance and PHT/FOS dose adjustments are recommended to ensure adequate and sustained tPHT serum levels early in treatment. Free serum PHT level is the preferred method of drug monitoring.