Alvarez N
Clin Electroencephalogr. 1985 Apr;16(2):104-10. doi: 10.1177/155005948501600210.
In the course of a large prospective study aimed at evaluating the efficacy of Valproic Acid (VPA) in persons with intractable seizures, six patients that were on a steady dose of diphenylhydantoin (DPH) were exposed to different steady doses of VPA. The changes observed in the serum levels of total, free, and percentage of free DPH are reported here. There were no consistent changes in the serum levels of total DPH, but when serum levels of DPH, obtained before VPA was added to the therapeutic plan, were considered, it was found that the total DPH decreased in those patients with the higher baseline levels while it increased in those with the lower baseline levels. There also was an increase in the absolute total and the percentage of free DPH in most instances. The data suggested that the changes occurred soon after VPA was added and remained constant in the same patient as long as the total dose of VPA did not change. The data also suggested that VPA most probably interfered through a dual mechanism, displacement of albumin-fixed DPH, and decreased liver clearance of DPH. The interpersonal variability was such that only broad generalizations are possible. There is a need to measure free DPH in patients on VPA.
在一项旨在评估丙戊酸（VPA）对难治性癫痫患者疗效的大型前瞻性研究过程中，六名正在服用稳定剂量苯妥英（DPH）的患者接受了不同稳定剂量的VPA治疗。本文报告了总DPH、游离DPH及其游离百分比血清水平的变化情况。总DPH血清水平没有一致的变化，但如果考虑在将VPA添加到治疗方案之前测得的DPH血清水平，就会发现基线水平较高的患者总DPH降低，而基线水平较低的患者总DPH升高。在大多数情况下，游离DPH的绝对总量及其百分比也有所增加。数据表明，这些变化在添加VPA后很快就会出现，并且只要VPA的总剂量不变，同一名患者的这些变化就会保持稳定。数据还表明，VPA很可能通过双重机制产生干扰，即置换白蛋白结合的DPH以及降低肝脏对DPH的清除率。个体差异很大，只能进行宽泛的概括。有必要对服用VPA的患者测量游离DPH。
