Campbell N R, Hasinoff B B, Robertson S, Singh M
Department of Medicine, Faculty of Medicine, University of Calgary, Alberta.
Clin Invest Med. 1993 Aug;16(4):280-4.
A variety of drugs which bind to iron have significant reductions in absorption when co-administered with iron compounds. The chemical structure of phenytoin indicates that there may be possible binding to iron ions. In vitro experiments were performed to determine whether any binding of iron to phenytoin occurred, and in vivo studies examined the effect of ferrous sulfate on phenytoin absorption in an isolated perfused rat jejunal model of drug absorption. The dose of phenytoin was limited by solubility and represents a human dose of 28 mg on a mg/kg basis for the rat assuming the total dose to be in 10 cm bowel in the rat. The ferrous sulfate doses were chosen to represent 28 and 300 mg doses on a similar basis to phenytoin. There was no significant effect of ferrous sulfate on phenytoin absorption or instability of phenytoin in the presence of ferrous sulfate in the rat. In vitro experiments indicated that little or no phenytoin binding to iron occurred. Results from animal model studies using low doses of phenytoin suggest it is unlikely that there will be a significant reduction in phenytoin absorption during concurrent therapy with iron salts.
多种与铁结合的药物在与铁化合物共同给药时，其吸收会显著降低。苯妥英的化学结构表明它可能与铁离子发生结合。进行了体外实验以确定铁是否会与苯妥英发生结合，并且在体内研究中，在一个分离灌注的大鼠空肠药物吸收模型中考察了硫酸亚铁对苯妥英吸收的影响。苯妥英的剂量受溶解度限制，按毫克/千克计算，对于大鼠而言相当于人体剂量28毫克，假设总剂量存在于大鼠10厘米长的肠段中。硫酸亚铁的剂量选择为在与苯妥英相似的基础上分别代表28毫克和300毫克的剂量。在大鼠中，硫酸亚铁对苯妥英的吸收或在硫酸亚铁存在下苯妥英的稳定性没有显著影响。体外实验表明，苯妥英与铁几乎不发生或不发生结合。使用低剂量苯妥英的动物模型研究结果表明，在与铁盐同时治疗期间，苯妥英的吸收不太可能显著降低。
