Department of Neurology, Strong Epilepsy Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Department of Biostatistics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Seizure. 2017 Nov;52:199-204. doi: 10.1016/j.seizure.2017.10.006. Epub 2017 Oct 16.
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.
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.
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.
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.
由于苯妥英（PHT）和磷苯妥英（FOS）的药代动力学特征复杂，在使用的第一天达到持续、靶向的血清 PHT 水平具有挑战性。
在急性医院环境中，采用基于人群的方法分析 PHT/FOS 负荷剂量后 2-24 小时内 PHT 初治患者的总血清 PHT（tPHT）水平，有无补充维持剂量或额外负荷剂量。适当的 tPHT 血清水平定义为≥20μg/mL。
在 494 例患者的 545 个负荷剂量后 2-24 小时内获得的 tPHT 血清水平中，观察到 tPHT 血清水平<或≥20μg/mL 的患者分布在广泛重叠的累积剂量范围内。在接受 15-20mg/kg 和 20-55mg/kg 体重负荷剂量的患者中，分别有 63%和 51%的患者在治疗的前 6 小时内未能达到 tPHT 血清水平≥20μg/mL。在 393 个可获得的游离和总血清 PHT 水平中，相关性较弱，r=0.36。
建议密切监测实验室并调整 PHT/FOS 剂量，以确保在治疗早期达到足够和持续的 tPHT 血清水平。游离血清 PHT 水平是药物监测的首选方法。
