Vecht Charles J, Wagner G Louis, Wilms Erik B
Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.
Semin Oncol. 2003 Dec;30(6 Suppl 19):49-52. doi: 10.1053/j.seminoncol.2003.11.030.
Seizures are a common complication in patients with primary brain tumors or brain metastases that require treatment with antiepileptic drugs (AEDs). However, because many AEDs and chemotherapeutics share common metabolic pathways via the hepatic cytochrome P450 (CYP) isoenzymes, there is potential for drug interactions. Phenytoin, carbamazepine, and phenobarbital are potent enzyme-inducing AEDs (EIAEDs) that can cause a decrease in the serum concentration of chemotherapeutics, potentially compromising antitumor activity. Likewise, chemotherapeutics can alter the pharmacokinetics of EIAEDs, resulting in decreased seizure control. Other agents, such as valproic acid, are enzyme-inhibiting AEDs that can impede the metabolism of other drugs, potentially increasing the serum concentration of chemotherapeutics. Therefore, patients receiving valproic acid with concomitant chemotherapy should be monitored closely. A new generation of AEDs that are not metabolized by CYP isoenzymes is currently being developed. Of these, gabapentin and levetiracetam show the most promise in treating epileptic seizures in patients with brain tumors. Interactions between these newer AEDs and chemotherapeutic agents have not been reported. In summary, the potential interactions between AEDs and chemotherapy should be anticipated and appropriate proactive adjustments implemented. Future studies will define the role of newer AEDs in the treatment of patients with primary brain tumors.
癫痫发作是原发性脑肿瘤或脑转移瘤患者常见的并发症，这些患者需要使用抗癫痫药物（AEDs）进行治疗。然而，由于许多AEDs和化疗药物通过肝脏细胞色素P450（CYP）同工酶共享共同的代谢途径，因此存在药物相互作用的可能性。苯妥英、卡马西平和苯巴比妥是强效的酶诱导性抗癫痫药物（EIAEDs），可导致化疗药物的血清浓度降低，可能会损害抗肿瘤活性。同样，化疗药物可改变EIAEDs的药代动力学，导致癫痫控制效果降低。其他药物，如丙戊酸，是酶抑制性抗癫痫药物，可阻碍其他药物的代谢，可能会增加化疗药物的血清浓度。因此，接受丙戊酸并同时进行化疗的患者应密切监测。目前正在研发新一代不通过CYP同工酶代谢的AEDs。其中，加巴喷丁和左乙拉西坦在治疗脑肿瘤患者的癫痫发作方面显示出最大的前景。尚未报道这些新型AEDs与化疗药物之间的相互作用。总之，应预期AEDs与化疗之间的潜在相互作用，并进行适当的主动调整。未来的研究将确定新型AEDs在原发性脑肿瘤患者治疗中的作用。
