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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 2-24h 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 ≥20μg/mL.
RESULTS: Among 494 patients with 545 tPHT serum levels obtained in the first 2-24h after the loading dose (LD), tPHT serum levels of either <or≥20μg/mL were observed along wide and overlapping cumulative dose ranges. Among those receiving 15-20mg/kg and 20-55mg/kg weight-based loading dose, 63% and 51% respectively did not attain tPHT serum level of ≥20μg/mL even within the first 6h 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.
METHODS: A population based approach was used to analyze total serum PHT (tPHT) level within 2-24h 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 ≥20μg/mL.
RESULTS: Among 494 patients with 545 tPHT serum levels obtained in the first 2-24h after the loading dose (LD), tPHT serum levels of either <or≥20μg/mL were observed along wide and overlapping cumulative dose ranges. Among those receiving 15-20mg/kg and 20-55mg/kg weight-based loading dose, 63% and 51% respectively did not attain tPHT serum level of ≥20μg/mL even within the first 6h 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.
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