Johannessen Landmark Cecilie, Svendsen Torleiv, Dinarevic Jasmin, Kufaas Ruben F, Reimers Arne, Brodtkorb Eylert, Baftiu Arton, Burns Margrete L, Johannessen Svein I
*Department of Life Sciences and Health, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences; †The National Center for Epilepsy, Sandvika; ‡Department of Pharmacology, Oslo University Hospital; §Department of Neurology, Innlandet Hospital Trust, Lillehammer; ¶Department of Clinical Pharmacology, St. Olavs University Hospital; ‖Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine; and **Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Ther Drug Monit. 2016 Aug;38(4):499-505. doi: 10.1097/FTD.0000000000000306.
Eslicarbazepine acetate (ESL) is a new anti-epileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ.
Anonymous data regarding age, gender, use of AEDs, daily doses and serum concentration measurements of ESL, OXC, CBZ and lamotrigine (LTG) and other AEDs were retrieved from 2 therapeutic drug monitoring (TDM) databases in Norway. Drugs were categorized according to their known potential for interactions. Concentration/dose (C/D) ratios were calculated.
Data from 1100 patients were available. The C/D ratios of ESL and OXC were unchanged in combination with enzyme-inducing AEDs or valproate (VPA). The C/D ratio of CBZ decreased by 40% and 22% in combination with other enzyme-inducing AEDs or VPA, respectively, pointing to an increased clearance. ESL demonstrated no significant enzyme-inducing effect on LTG metabolism although there was a 20% and 34% decrease in the C/D ratio of LTG in combination with OXC and CBZ, respectively.
Possible pharmacokinetic interactions have been studied for ESL as compared to OXC and CBZ. The pharmacokinetics of ESL is not affected by enzyme-inducing AEDs or VPA and does not affect the metabolism of LTG in contrast to OXC and CBZ. The study demonstrates the value of using TDM databases to explore the potential for pharmacokinetic interactions of new AEDs.
醋酸艾司利卡西平（ESL）是一种新型抗癫痫药物（AED），在化学结构上与奥卡西平（OXC）和卡马西平（CBZ）相关，且在临床实践中的应用日益广泛。本研究旨在探讨ESL与其他AED之间的双向药代动力学相互作用，并与OXC和CBZ进行比较。
从挪威的两个治疗药物监测（TDM）数据库中检索有关年龄、性别、AED使用情况、ESL、OXC、CBZ和拉莫三嗪（LTG）以及其他AED的每日剂量和血清浓度测量的匿名数据。根据药物已知的相互作用潜力进行分类。计算浓度/剂量（C/D）比。
获得了1100例患者的数据。ESL和OXC与酶诱导性AED或丙戊酸盐（VPA）联合使用时，其C/D比未发生变化。CBZ与其他酶诱导性AED或VPA联合使用时，其C/D比分别降低了40%和22%，表明清除率增加。尽管LTG与OXC和CBZ联合使用时其C/D比分别降低了20%和34%，但ESL对LTG代谢未显示出明显的酶诱导作用。
已对ESL与OXC和CBZ相比可能存在的药代动力学相互作用进行了研究。与OXC和CBZ不同，ESL的药代动力学不受酶诱导性AED或VPA的影响，也不影响LTG的代谢。该研究证明了利用TDM数据库探索新型AED药代动力学相互作用潜力的价值。
