Phenytoin (brand name Dilantin) is an anticonvulsant medication used for the treatment of seizures (1). Phenytoin has a narrow therapeutic index—individuals that have supratherapeutic blood concentrations of phenytoin have increased risks of acute side effects. Dosing can be complex due to pharmacokinetic factors, including individual weight, age, gender, concomitant medications, plasma binding protein status, the presence of uremia or hyperbilirubinemia, and specific pharmacogenetic variants. As such, therapeutic drug monitoring is often used to adjust dose and maintain serum concentrations within the therapeutic range (10–20 μg/mL). The CYP2C9 enzyme is one of the main enzymes involved in the metabolism of phenytoin, and variant alleles are known to influence phenytoin drug levels. Individuals who have decreased activity variants may have reduced clearance rates of phenytoin and be at greater risk for dose-related side effects (2). An individual’s human leukocyte antigen B () genotype is a known risk factor for drug-induced hypersensitivity reactions. The HLA-B protein has an important immunological role in pathogen recognition and response, as well as to non-pathogens such as drugs. Individuals who have the allele are at high risk of developing potentially life-threatening phenytoin-induced Stevens-Johnson syndrome (SJS) and the related toxic epidermal necrolysis (TEN). The allele is most often found among individuals of Southeast Asian descent, where there is a strong association between SJS/TEN and exposure to carbamazepine. Carbamazepine is an antiseizure medication used to treat the same types of seizures as phenytoin, as well as trigeminal neuralgia and bipolar disorder. The FDA-approved drug label for phenytoin states that consideration should be given to avoiding phenytoin as an alternative for carbamazepine in individuals positive for (Table 1). The label also mentions that variant alleles may contribute to unusually high levels of phenytoin (1). Dosing recommendations for phenytoin based on and genotype have also been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC, Table 2, Figure 1) and the Dutch Pharmacogenetics Working Group (DPWG, Table 3, Table 4). These recommendations include the use of an antiseizure medication other than carbamazepine, phenytoin (or its prodrug fosphenytoin) for any positive individual regardless of genotype, individual ancestry, or age. These recommendations also include specific dose reductions of phenytoin for individuals who have low or deficient enzyme activity (2, 3).
苯妥英钠（商品名大仑丁）是一种用于治疗癫痫发作的抗惊厥药物（1）。苯妥英钠的治疗指数较窄——苯妥英钠血药浓度超过治疗范围的个体出现急性副作用的风险增加。由于药代动力学因素，给药可能很复杂，这些因素包括个体体重、年龄、性别、合并用药、血浆结合蛋白状态、尿毒症或高胆红素血症的存在以及特定的药物遗传学变异。因此，治疗药物监测常被用于调整剂量并将血清浓度维持在治疗范围内（10 - 20μg/mL）。CYP2C9酶是参与苯妥英钠代谢的主要酶之一，已知变异等位基因会影响苯妥英钠的药物水平。活性降低变异的个体可能苯妥英钠清除率降低，发生剂量相关副作用的风险更高（2）。个体的人类白细胞抗原B（）基因型是药物诱导的超敏反应的已知危险因素。HLA - B蛋白在病原体识别和反应以及对药物等非病原体的反应中具有重要的免疫作用。携带等位基因的个体发生潜在危及生命的苯妥英钠诱导的史蒂文斯 - 约翰逊综合征（SJS）及相关的中毒性表皮坏死松解症（TEN）的风险很高。等位基因在东南亚裔个体中最常见，在这些个体中，SJS/TEN与卡马西平暴露之间存在很强的关联。卡马西平是一种抗癫痫药物，用于治疗与苯妥英钠相同类型的癫痫发作，以及三叉神经痛和双相情感障碍。美国食品药品监督管理局（FDA）批准的苯妥英钠药物标签指出，对于携带的个体，应考虑避免将苯妥英钠作为卡马西平的替代品（表1）。该标签还提到变异等位基因可能导致苯妥英钠水平异常升高（1）。临床药物遗传学实施联盟（CPIC，表2，图1）和荷兰药物遗传学工作组（DPWG，表3，表4）也发布了基于和基因型的苯妥英钠给药建议。这些建议包括对于任何携带的个体，无论其基因型、个体血统或年龄如何，都应使用除卡马西平、苯妥英钠（或其前体药物磷苯妥英）之外的抗癫痫药物。这些建议还包括针对酶活性低或缺乏的个体对苯妥英钠进行特定的剂量减少（2, 3）。
