Berg M J, Stumbo P J, Chenard C A, Fincham R W, Schneider P J, Schottelius D D
College of Pharmacy, University of Iowa, Iowa City 52242.
J Am Diet Assoc. 1995 Mar;95(3):352-6. doi: 10.1016/s0002-8223(95)00090-9.
Phenytoin (PHT) therapy to control seizures decreases serum folate levels in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but also changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic acid is provided as a supplement has not been reported in women of child-bearing age. This study of six fertile women examined the interdependence of PHT and folic acid in a randomized crossover study of two treatments: treatment 1 consisted of 300 mg sodium PHT per day and treatment 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Dietary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0 +/- 18.6% (mean +/- standard deviation) and serum PHT concentration was in the low therapeutic range (43.92 +/- 14.52 mumol/L). During treatment 2, serum folate level increased 26.0 +/- 33.4%, and serum PHT level (39.04 +/- 14.16 mumol/L) was similar to that in treatment 1. Only one subject attained PHT steady state during treatment 1, but four subjects achieved steady state during treatment 2. Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.
用于控制癫痫发作的苯妥英（PHT）治疗会使一半癫痫患者的血清叶酸水平降低，从而增加叶酸缺乏的风险。补充叶酸可预防缺乏，但也会改变PHT的药代动力学。在育龄女性中，尚未有关于补充叶酸时PHT动力学监测的报道。这项针对六名育龄女性的研究，在一项两种治疗方法的随机交叉研究中，检测了PHT和叶酸之间的相互依存关系：治疗1为每日300毫克苯妥英钠，治疗2为每日300毫克苯妥英钠加1毫克叶酸。每日计算膳食叶酸摄入量。在治疗1期间，血清叶酸水平下降了38.0 +/- 18.6%（平均值 +/- 标准差），血清PHT浓度处于低治疗范围（43.92 +/- 14.52微摩尔/升）。在治疗2期间，血清叶酸水平上升了26.0 +/- 33.4%，血清PHT水平（39.04 +/- 14.16微摩尔/升）与治疗1相似。治疗1期间只有一名受试者达到PHT稳态，但治疗2期间有四名受试者达到稳态。治疗1和治疗2期间的膳食叶酸摄入量无显著差异。这项研究表明PHT和叶酸之间存在相互依存关系，并支持以下观察结果：接受PHT治疗的育龄女性需要补充叶酸以维持正常的血清叶酸水平。
