Berbel Garcia A, Latorre Ibarra A, Porta Etessam J, Martinez Salio A, Perez Martinez D, Siaz Diaz R, Toledo Heras M
Department of Neurology, Hospital 12 de Octubre, Madrid, Spain.
Clin Neuropharmacol. 2000 Jul-Aug;23(4):216-8. doi: 10.1097/00002826-200007000-00009.
Neurologic manifestations of HIV infection are quite diverse and can develop into seizures. Because new drug therapies have been developed, it is important to know the interactions between antiretroviral and antiepileptic agents. A 36-year-old patient with HIV developed a set of progressive left hemiparesis and secondarily generalized partial seizures related to progressive multifocal leukoencephalopathy. Phenytoin and carbamazepine were necessary to control the seizures. Instead of diverse antiretroviral therapies, the viral load was increased. Protease inhibitors (ritonavir and saquinavir) were added to the treatment and the patient developed progressive ataxia related to carbamazepine toxicity. Carbamazepine was discontinued and the patient remained asymptomatic. The patient was diagnosed with carbamazepine toxicity related to the introduction of ritonavir. Ritonavir is a potent inhibitor of hepatic cytochrome P450, mainly the CYP3A4 isoform. Carbamazepine is metabolized by this subsystem. Ritonavir acted as a CYP3A4 inhibitor, diminishing carbamazepine metabolism and provoking an increase in serum levels and clinical toxicity. We present a case of interaction between ritonavir and carbamazepine. Interaction between antiepileptic and antiretroviral agents is an emergent problem caused by the increasing association of the two therapies. We recommend strict monitoring of serum antiepileptic drug (AED) levels to avoid toxicity and inadequate seizure control.
HIV感染的神经系统表现多种多样，且可能发展为癫痫发作。由于已开发出新的药物疗法，了解抗逆转录病毒药物与抗癫痫药物之间的相互作用很重要。一名36岁的HIV患者出现了一系列与进行性多灶性白质脑病相关的进行性左侧偏瘫和继发性全身性部分性癫痫发作。苯妥英钠和卡马西平对于控制癫痫发作是必要的。与采用多种抗逆转录病毒疗法不同，病毒载量增加了。于是在治疗中添加了蛋白酶抑制剂（利托那韦和沙奎那韦），患者出现了与卡马西平毒性相关的进行性共济失调。停用卡马西平后患者保持无症状。该患者被诊断为与引入利托那韦相关的卡马西平毒性。利托那韦是肝细胞色素P450的强效抑制剂，主要是CYP3A4亚型。卡马西平由该亚系统代谢。利托那韦作为CYP3A4抑制剂，减少了卡马西平的代谢，导致血清水平升高和临床毒性。我们报告了一例利托那韦与卡马西平相互作用的病例。抗癫痫药物与抗逆转录病毒药物之间的相互作用是由这两种疗法日益联合使用所引发的一个新出现的问题。我们建议严格监测血清抗癫痫药物（AED）水平，以避免毒性反应和癫痫控制不佳。
