University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD, USA.
University of Maryland School of Pharmacy, 20 N Pine St, Baltimore, MD, USA.
Drugs R D. 2020 Mar;20(1):17-22. doi: 10.1007/s40268-019-00292-1.
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.
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.
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).
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.
本研究旨在确定目前计算磷苯妥英重剂量的方法是否会在随后的几天内达到治疗性游离苯妥英水平。
筛选了 2017 年 7 月至 2018 年 6 月在神经危重病护理单元接受磷苯妥英治疗的患者的病历。纳入标准为至少接受过 3 剂磷苯妥英治疗且根据治疗药物监测获得的浓度需要重剂量的患者。游离苯妥英水平根据预设的患者特异性靶范围进行分类，通常在 1.5 至 2.5mcg/mL 之间。
在给予的磷苯妥英重剂量中，48%（73/152）在随后的一天达到治疗性游离苯妥英浓度，其余 52%则导致非治疗性水平（39%治疗性水平，13%治疗性水平）。我们对重剂量计算策略的评估表明，当省略使用分布容积或盐形式的改良药代动力学方程时，患者获得治疗性水平的可能性是使用当前药代动力学模型（58%，n=39）的两倍，而不是使用当前药代动力学模型（41%，n=20）或根据提供者偏好计算的剂量（39%，n=14）。
目前在危重病患者中计算磷苯妥英重剂量的方法并不能始终达到治疗浓度。由于多种因素影响危重病患者的药代动力学，因此创建一个较少强调分布容积的新药代动力学模型可能更能持续达到治疗浓度。
