Perucca E, Richens A
Drugs. 1981 Feb;21(2):120-37. doi: 10.2165/00003495-198121020-00003.
Drug interactions with phenytoin are a frequent occurrence, although their clinical relevance has often been overemphasised. Probably the most important of such interactions are those resulting in inhibition of phenytoin metabolism: due to the saturable nature of phenytoin biotransformation even minor degrees of inhibition can produce disproportionate changes in both steady-state serum concentration and the magnitude of pharmacological effect. Phenytoin has marked enzyme-inducing properties and can stimulate the metabolism of many concurrently administered drugs, thereby reducing their therapeutic efficacy. Clinically important examples of such interactions include a reduction of the anticoagulant effect of dicoumarol, a decrease in the prophylactic efficacy of the contraceptive pill and failure of response to various corticosteroid agents when administered therapeutically or diagnostically. Unless complicated by additional mechanisms, plasma protein binding interactions with phenytoin are seldom of clinical significance. However, they may alter considerably the relationship between serum drug concentration and clinical response, a possibility which needs to be taken into account when interpreting serum phenytoin levels in clinical practice.
苯妥英钠的药物相互作用很常见，尽管其临床相关性常常被过度强调。这类相互作用中可能最重要的是那些导致苯妥英钠代谢受抑制的情况：由于苯妥英钠生物转化具有饱和性，即使是轻微程度的抑制也会使稳态血清浓度和药理效应强度产生不成比例的变化。苯妥英钠具有显著的酶诱导特性，可刺激许多同时服用药物的代谢，从而降低它们的治疗效果。这类相互作用在临床上的重要例子包括双香豆素抗凝作用减弱、避孕药预防效果降低以及治疗或诊断性使用各种皮质类固醇药物时无反应。除非有其他机制的复杂影响，与苯妥英钠的血浆蛋白结合相互作用很少具有临床意义。然而，它们可能会显著改变血清药物浓度与临床反应之间的关系，在临床实践中解读血清苯妥英水平时需要考虑到这种可能性。
