Markowsky S J, Skaar D J, Christie J M, Eyer S D, Ehresman D J
Merck & Company, Tampa, FL, USA.
Ann Pharmacother. 1996 May;30(5):443-8. doi: 10.1177/106002809603000501.
To longitudinally evaluate unbound and total serum phenytoin concentrations during intravenous phenytoin maintenance dosage and to determine the relationship among phenytoin protein binding, serum albumin, and unbound fatty acid concentrations in patients with head injuries during intensive care unit (ICU) and convalescent care.
Serum albumin and phenytoin unbound fraction were determined twice weekly during ICU and convalescent care in 10 patients receiving phenytoin following acute brain injury. Phenytoin protein binding was also determined in 10 healthy control subjects.
Longitudinal serum phenytoin concentrations associated with dosage adjustments targeted to achieve unbound phenytoin serum concentrations between 1.0 and 2.0 mg/L were documented during ICU and convalescent care. Longitudinal phenytoin binding was correlated with serum albumin and unbound fatty acid concentrations in neurotrauma patients.
ICU patients received intravenous therapy for a mean of 15.0 days. The mean +/- SD initial phenytoin intravenous dosage regimen of 6.0 +/- 0.7 mg/kg/d resulted in mean +/- SD total and unbound phenytoin concentrations of 3.2 +/- 2.3 and 0.3 +/- 0.2 mg/L. Two patients had seizures associated with low phenytoin concentrations. Four patients continued to receive oral phenytoin therapy during convalescent care; phenytoin dosage requirements decreased over time in these patients. During acute and convalescent care, the phenytoin unbound fraction ranged from 6.0% to 18.3% and correlated with albumin (r2 = 0.61, p < 0.0001) but did not correlate with unbound fatty acid concentrations. The mean phenytoin unbound fraction was 10.1% and 8.9% for the ICU and convalescent patients with brain injuries, respectively, and was 7.0% for the healthy volunteers.
Phenytoin protein binding was significantly correlated with albumin and was more variable in ICU and convalescent patients with brain injuries than in healthy volunteers. The high dosage requirements and subtherapeutic unbound phenytoin concentrations observed during acute care are best explained by increased metabolism. Phenytoin dosage requirements decreased during convalescence.
纵向评估静脉注射苯妥英维持剂量期间血清中游离苯妥英和总苯妥英的浓度，并确定重症监护病房（ICU）和康复护理期间头部受伤患者的苯妥英蛋白结合、血清白蛋白和游离脂肪酸浓度之间的关系。
在10例急性脑损伤后接受苯妥英治疗的患者的ICU和康复护理期间，每周测定两次血清白蛋白和苯妥英游离分数。还测定了10名健康对照者的苯妥英蛋白结合情况。
记录ICU和康复护理期间与剂量调整相关的纵向血清苯妥英浓度，目标是使游离苯妥英血清浓度达到1.0至2.0mg/L。神经创伤患者的纵向苯妥英结合与血清白蛋白和游离脂肪酸浓度相关。
ICU患者接受静脉治疗的平均时间为15.0天。初始苯妥英静脉给药方案的平均±标准差为6.0±0.7mg/kg/d，导致总苯妥英和游离苯妥英浓度的平均±标准差分别为3.2±2.3和0.3±0.2mg/L。两名患者出现与苯妥英浓度低相关的癫痫发作。四名患者在康复护理期间继续接受苯妥英口服治疗；这些患者的苯妥英剂量需求随时间下降。在急性和康复护理期间，苯妥英游离分数在6.0%至18.3%之间，与白蛋白相关（r2 = 0.61，p < 0.0001），但与游离脂肪酸浓度无关。脑损伤的ICU患者和康复患者的苯妥英平均游离分数分别为10.1%和8.9%，健康志愿者为7.0%。
苯妥英蛋白结合与白蛋白显著相关，在脑损伤的ICU患者和康复患者中比在健康志愿者中更具变异性。急性护理期间观察到的高剂量需求和游离苯妥英浓度低于治疗水平，最好用代谢增加来解释。康复期间苯妥英剂量需求下降。
