Bruni J, Gallo J M, Lee C S, Perchalski R J, Wilder B J
Neurology. 1980 Nov;30(11):1233-6. doi: 10.1212/wnl.30.11.1233.
The interaction of phenytoin and valproic acid was studied in four adults. We studied serial changes in total phenytoin concentrations, protein binding, urinary hydroxyphenylphenylhydantoin (HPPH) excretion, and half-life. In all four patients valproic acid caused an increase in the free fraction of phenytoin. Total phenytoin plasma concentrations decreased transiently in three patients and remained low throughout the study period in one patient. HPPH excretion increased transiently and then decreased, corresponding to changes in total phenytoin plasma concentrations. Biologic half-life transiently decreased in three patients (not statistically significant) and subsequently increased significantly in all four patients. The data suggest that valproic acid displaced phenytoin from protein-binding sites in all four patients and subsequently inhibited phenytoin metabolism in three patients.
在四名成年人中研究了苯妥英钠与丙戊酸的相互作用。我们研究了苯妥英钠总浓度、蛋白结合、尿中羟基苯基苯妥英（HPPH）排泄及半衰期的系列变化。在所有四名患者中，丙戊酸均导致苯妥英钠游离分数增加。三名患者的苯妥英钠血浆总浓度短暂下降，一名患者在整个研究期间均保持较低水平。HPPH排泄先短暂增加然后下降，与苯妥英钠血浆总浓度的变化相对应。三名患者的生物半衰期短暂下降（无统计学意义），随后所有四名患者的生物半衰期均显著增加。数据表明，在所有四名患者中丙戊酸使苯妥英钠从蛋白结合位点上被置换出来，随后在三名患者中抑制了苯妥英钠的代谢。
