Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Siriraj Poison Control Center, Bangkok, Thailand.
Ther Drug Monit. 2023 Oct 1;45(5):573-575. doi: 10.1097/FTD.0000000000001129.
Phenytoin is commonly prescribed to prevent postoperative seizures. Despite the rarity of the CYP2C9 genetic polymorphism, which may result in poor phenytoin metabolism, in the Thai population, the authors report a case of phenytoin toxicity in a patient with poor metabolism administered with a standard dose of phenytoin.
A 58-year-old Thai woman presented to the outpatient clinic with a 2-day history of nausea, vomiting, and dizziness. She underwent craniotomy for tumor removal 2 weeks after being diagnosed with tuberculum sellae meningioma. After the surgery, she was prescribed 300 mg of phenytoin daily to prevent seizures. During the physical examination, ataxia, horizontal nystagmus, and cerebellar abnormalities were observed, with an initial serum phenytoin concentration of 58.85 mg/L. The brain imaging results were unremarkable. Omeprazole was the only recognized drug interaction; however, it is highly unlikely to account for this condition. Pharmacogenetic investigation of CYP2C9 revealed a homozygous CYP2C9*3/*3 mutation, which is indicative of suboptimal drug metabolism and can reduce phenytoin metabolism by 50%. This patient was administered repeated dosages of activated charcoal over the course of 2 days. Her symptoms eventually subsided, with the phenytoin levels dropping to 29.51 mg/L.
In the absence of an overdose history or drug-drug interaction, CYP2C9 polymorphism should be suspected in patients with phenytoin toxicity. In such situations, the phenytoin dosage must be decreased and monitored closely.
苯妥英通常用于预防术后癫痫发作。尽管 CYP2C9 基因多态性在泰国人群中罕见,可能导致苯妥英代谢不良,但作者报告了一例代谢不良患者给予标准剂量苯妥英后发生苯妥英中毒的病例。
一名 58 岁泰国女性因恶心、呕吐和头晕就诊于门诊,她在被诊断为鞍结节脑膜瘤后 2 周接受了颅切除术。手术后,她每天服用 300 毫克苯妥英以预防癫痫发作。在体格检查中,观察到共济失调、水平性眼球震颤和小脑异常,初始血清苯妥英浓度为 58.85 毫克/升。脑部影像学结果无明显异常。仅发现奥美拉唑是一种公认的药物相互作用,但不太可能导致这种情况。CYP2C9 的药物遗传学研究显示为 CYP2C9*3/*3 纯合突变,表明药物代谢不佳,可使苯妥英代谢减少 50%。该患者接受了 2 天重复剂量的活性炭治疗。她的症状最终缓解,苯妥英水平降至 29.51 毫克/升。
在没有用药过量史或药物-药物相互作用的情况下,应怀疑苯妥英中毒患者存在 CYP2C9 多态性。在这种情况下,必须减少苯妥英剂量并密切监测。