Berg M J, Ebert B E, Rivey M P, Schottelius D D
College of Pharmacy, University of Iowa, Iowa City 52242.
Ther Drug Monit. 1987 Sep;9(3):304-5. doi: 10.1097/00007691-198709000-00009.
Phenytoin decreases serum and red blood cell folates in 50% of the patients on the anticonvulsant. The supplementation of folic acid changes the disposition of phenytoin, a drug that exhibits Michaelis-Menten kinetics. In a retrospective study at the Veterans Administration Medical Center, seven adult male folate-deficient epileptic patients on phenytoin alone and compliant with the anticonvulsant were supplemented with 1 mg oral folic acid. Before and after the addition of the vitamin, Vmax and Km were calculated for phenytoin. With folic acid, the total serum phenytoin concentration decreased significantly by an average of 22.6 +/- 13.0%. The Km decreased significantly from 6.7 +/- 1.1 to 4.1 +/- 1.5 micrograms/ml. The Vmax remained unchanged. It is hypothesized that folic acid is a cofactor in the metabolism of phenytoin. A cofactor would be expected to alter the affinity (Km) of the enzymes for phenytoin with no change in the liver's total capacity (Vmax) to metabolize phenytoin. This retrospective study in seven male epileptic patients is a convincing argument for the hypothesis.
苯妥英会使50%服用该抗惊厥药物的患者血清和红细胞中的叶酸水平降低。补充叶酸会改变苯妥英（一种呈现米氏动力学的药物）的代谢情况。在退伍军人管理局医疗中心进行的一项回顾性研究中，七名成年男性叶酸缺乏的癫痫患者，仅服用苯妥英且遵守抗惊厥药物治疗方案，他们口服了1毫克叶酸进行补充。在添加维生素前后，计算苯妥英的最大反应速度（Vmax）和米氏常数（Km）。服用叶酸后，血清苯妥英总浓度显著下降，平均下降了22.6±13.0%。Km从6.7±1.1显著降至4.1±1.5微克/毫升。Vmax保持不变。据推测，叶酸是苯妥英代谢中的一种辅助因子。预计辅助因子会改变酶对苯妥英的亲和力（Km），而肝脏代谢苯妥英的总能力（Vmax）不变。这项针对七名男性癫痫患者的回顾性研究有力地支持了这一假设。
