Lewis D P, Van Dyke D C, Willhite L A, Stumbo P J, Berg M J
College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Ann Pharmacother. 1995 Jul-Aug;29(7-8):726-35. doi: 10.1177/106002809502907-816.
To review information regarding the dual and interdependent drug-nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid.
Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references.
All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction.
Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events.
Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the "pseudo-steady-state," which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner.
Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.
回顾有关苯妥英钠与叶酸之间双重且相互依存的药物 - 营养相互作用的信息以及其他涉及苯妥英钠和叶酸的文献。
从1983年（上次综述时间）至1995年3月进行的MEDLINE英文文献检索中获取信息。检索词包括叶酸、苯妥英钠和叶酸缺乏。其他参考文献从《现刊目次》以及检索到的参考文献的 bibliography 中获取。
选取了所有研究苯妥英钠对血清叶酸浓度的影响以及叶酸补充对血清苯妥英钠浓度影响的人体研究。这些研究包括癫痫患者和健康志愿者的研究以及病例报告。纳入病例报告是因为研究这种药物相互作用需要很长时间。
提取的数据包括性别、给药剂量、血清叶酸浓度（如可得）、药代动力学和不良事件。
单独开始苯妥英钠治疗且不补充叶酸时，血清叶酸会降低。癫痫叶酸缺乏患者补充叶酸会改变苯妥英钠的药代动力学，通常导致血清苯妥英钠浓度降低并可能出现癫痫发作突破。据推测，叶酸是苯妥英钠代谢的辅助因子，可能是“假稳态”的原因，“假稳态”是指苯妥英钠看似处于稳态，但实际上并非如此的浓度。同时开始苯妥英钠和叶酸治疗可防止叶酸降低，且苯妥英钠能更快达到稳态浓度。
由于推测的辅助因子机制、叶酸缺乏相关不良影响的减少以及在不干扰苯妥英钠药代动力学的情况下更好地控制癫痫发作，每次开始苯妥英钠治疗时都应开始补充叶酸。
