卡马西平、托吡酯与丙戊酸钠治疗201例脑炎继发癫痫疗效分析

目的：对卡马西平(CBZ)、托吡酯(TPM)和丙戊酸钠缓释片(VPA)在脑炎继发性癫痫疾病治疗中起到的作用及其负面作用进行分析。方法选取201例脑炎继发性癫痫患者,对其资料进行回顾分析,按用药不同分为VPA(71例)、TPM(61例)、CBZ(69例)三组,而后对其在接受了VPA、TPM及CBZ为期1年的治疗之后的疗效进行比较,从而对药物的负面作用做出评价。结果 CBZ对脑炎继发癫痫的总有效率为72.46%,和VPA的78.87%和TPM 80.33%的差异无统计学意义(P>0.05)。TPM不良反应率明显低于另外两组,差异有统计学意义(P<0.05)。结论在采取单一药物治疗手段时, CBZ在部分发作癫痫上的疗效可观,而TPM和VPA对所有类型的脑炎激发的癫痫均起到不错的疗效,而TPM的负面作用较其余两种更少。     

托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫效果分析

目的探讨托吡酯(TPM)、卡马西平(CBZ)与丙戊酸钠(VPA)治疗脑炎继发癫痫(SEVE)的效果。方法选取我院2012年2月~2014年2月的96例脑炎继发癫痫患者为研究对象,采用随机数字表法将其均分为TPM组、CBZ组和VPA组。TPM组采用托吡酯,CBZ组采用卡马西平,VPA组采用丙戊酸钠进行治疗,疗程均为1年,观察3组患者治疗后的临床疗效以及不良反应情况。结果治疗后TPM组、CBZ组和VPA组的总有效率分别为84.38%,78.13%,81.25%,3组差异均无统计学意义;而TPM组、CBZ组和VPA组的不良反应发生率分别为9.38%,37.50%,25.00%,差异具有统计学意义。结论托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫患者的临床效果确切,疗效间无差异,但是使用托吡酯的不良反应发生率明显低于卡马西平和丙戊酸钠。     

几种新癫痫药分别联合丙戊酸钠治疗难治性癫痫的对比

目的：探讨部分难治性癫痫（RE）在添加拉莫三嗪（LTG）或奥卡西平（OXC）或托吡酯（TPM）联合丙戊酸钠（VPA）治疗的临床疗效。方法累积收集2009年1月~2014年1月符合标准的212例难治性部分性癫痫患者,对照治疗3个月前癫痫发作频度,并对治疗2年结束后的疗效、不良反应（ADR）及安全性和脑电图进行自身分析对比。结果患者应用LTG或OXC或TPM联合VPA治疗RE 2年结束后,患者发作频率均比用药前明显减少,患者治疗结束后的总有效率分别为89%、88.5%、78.1%, ADR的发生率分别为9.6%、19.2%、21.9%,脑电图总的好转率分别为89.9%、78.5%、76.9%。结论 LTG或OXC或TPM联合VPA治疗RE患者的疗效确切,耐受性好,安全性高, ADR轻。     

奥卡西平治疗儿童青少年躁狂发作的疗效和安全性

目的 比较奥卡西平片与丙戊酸钠缓释片治疗儿童青少年躁狂发作的疗效和安全性.方法 将87例躁狂发作的儿童青少年患者,随机分为奥卡西平组(OXC组)44例,丙戊酸钠缓释片组(VPA组)43例.按滴定法达到最佳剂量进行系统治疗,治疗疗程为6周.以Young躁狂评定量表(YMRS)、临床总体印象量表-严重度(CGI-S)和治疗副反应量表(TESS)及有关实验室检查评定疗效和不良反应.结果 OXC和VPA治疗儿童青少年躁狂发作的YMRS评分均较治疗前降低(P均<0.05),且第1、2周末时OXC组评分下降更明显(P<0.05).OXC组和VPA组的痊愈率分别为44.44%和44.11%,有效率分别为80.55%和79.41%,两组的疗效差异不具有统计学意义(P>0.05).药物不良反应发生率相近,均为轻中度.结论 奥卡西平能有效治疗儿童青少年躁狂发作,且安全性较好.     

新型和传统抗癫痫药物治疗新诊断部分性癫痫的临床研究

目的:比较新型和传统抗癫痫药(AEDs)治疗新诊断部分性癫痫患者的疗效及安全性。方法:收集新诊断部分性癫痫患者的临床资料,分为卡马西平(carbamazepine, CBZ)组、左乙拉西坦(levetiracetam, LEV)组、奥卡西平(oxcarbazepine, OXC)组和拉莫三嗪(lamotrigine, LTG)组,以治疗后稳定期初次发作时间、治疗失败时间和达“6月、1年和2年无发作”比例为观察指标,评估其治疗癫痫的有效性及安全性。结果:本研究共收集250例新诊断部分性发作癫痫患者,分为CBZ组(n=62)、LEV组(n=67)、OXC组(n=63)、LTG组(n=58)。通过Kaplan-Meier统计分析显示新型和传统AEDs治疗癫痫后初次发作时间,CBZ和OXC的疗效相当(Log-Rank=0.226,P=0.635),而CBZ优于LTG(Log-Rank=15.305,P=0.000)和LEV(Log-Rank=8.027,P=0.005);治疗失败时间,CBZ和LTG疗效相当(Log-Rank=0.127,P=0.721),而CBZ优于OXC、LEV,差异均具有...     

新型抗癫痫药物治疗复杂部分性发作癫痫的保留率比较

目的:分别给予新诊断的复杂部分性发作癫痫患者不同的新型抗癫痫药单药治疗,比较4种抗癫痫新药的总有效率和一年保留率。方法:对253例新诊断的复杂部分性发作及复杂部分性发作继发全面性发作癫痫患者随机给予奥卡西平、托吡酯、左乙拉西坦、拉莫三嗪单药治疗,比较其总有效率和一年保留率,并分析停药原因。结果:4种抗癫痫新药控制癫痫的疗效基本一致,总有效率为75.4%～87.1%,无统计学差异。拉莫三嗪的保留率最高(88.6%),其次为左乙拉西坦(85.3%),托吡酯为68.5%,奥卡西平最低(61.4%)。拉莫三嗪与其他3种抗癫痫新药的保留率有统计学差异(P<0.05),其他3种药物之间无统计学差异。停药或换药的主要原因是癫痫控制无效或加重(28例,42.4%);其次是不良反应(13例,19.7%)及药物价格(10例,15.2%)。结论:4种抗癫痫新药的有效性无明显优劣差异,拉莫三嗪的一年保留率最高,停药原因主要为药物疗效不佳和不良反应。     

奥卡西平或卡马西平单药治疗部分性癫痫发作的Meta分析

目的:评价奥卡西平(OXC)和卡马西平(CBZ)治疗部分性癫痫发作疗效和安全性的差异。方法:在Cochrane图书馆、PubMed、中国医院数字图书馆上检索OXC和CBZ单药治疗部分性癫痫发作的随机对照试验(RCT),采用Meta分析专用软件RevMan 5.0.0进行系统评价。结果:共纳入5个RCT,454例部分性癫痫患者,其中A级文献3篇,C级2篇;Meta分析结果显示,OXC组和CBZ组治疗部分性癫痫的总控制率相当,2组比较差异无统计学意义[RR1.09,95%CI(0.73,1.64)];OXC组不良反应(ADR)发生率低于CBZ组[RR0.61,95%CI(0.41,0.91)];OXC组严重ADR退出率也低于CBZ组(RR0.51,95%CI(0.28,0.92))。结论:现有证据表明,OXC治疗部分性癫痫发作疗效并不优于CBZ,但前者安全性更好。     

妊娠期妇女新型抗癫痫药的药物浓度监测研究进展

目的:了解妊娠期妇女新型抗癫痫药拉莫三嗪(LTG)、左乙拉西坦(LEV)、托吡酯(TPM)和奥卡西平(OXC)的药物浓度监测的研究进展。方法:查阅近年来国内外相关文献,就LTG、LEV、TPM和OXC的药物浓度监测的研究进行归纳和总结。结果与结论:LTG、LEV、TPM和OXC在妊娠期的代谢率增加,血药浓度显著下降,部分患者癫痫发作频率增加,产后血药浓度迅速恢复至正常水平,但上述4种药物的具体变化情况存在差异,且个体差异显著。LTG、LEV、TPM和OXC在妊娠期血药浓度的下降可能与葡糖醛酸化作用增强和肾清除率增加相关,但显著的个体差异导致不能提前预测和预防。妊娠期血药浓度的下降不等于癫痫发作频率的增加,规律的药物浓度监测给剂量调整提供了证据支持。虽然仍缺乏LTG、LEV、TPM和OXC大范围适用的妊娠期有效的血药浓度推荐范围,仍建议在妊娠前获得癫痫患者血药浓度基线水平作为参考,确定个体化的有效血药浓度范围,妊娠各阶段至少各进行1次治疗药物的浓度监测,若癫痫发作增加则应及时测定血药浓度并调整剂量;产后1~2周进行治疗药物的浓度监测,逐渐减量恢复至基线水平。     

5种常用抗癫痫药物的临床使用情况及其血清浓度水平的分析及意义

目的 分析3种新型抗癫痫药物[奥卡西平(Oxcarbazepine, OXC)、左乙拉西坦(Levetiracetam, LEV)及拉莫三嗪(Lamotrigine, LTG)]和2种传统型抗癫痫药物[丙戊酸钠(Valproic acid, VPA)与卡马西平(Carbamazepine, CBZ)]临床使用情况及常规剂量用药后血清浓度水平,为新发癫痫患者进行药物治疗提供依据。方法 回顾性分析2018年1月至2021年12月在安徽中医药大学神经病学研究所附属医院进行抗癫痫药物治疗的1 261例癫痫患者治疗信息。按照用药模式分成4组,分别为单一用药、两药联合、三药联合及四药联合组;按性别分为男性、女性组;按年龄分成6组,分别为≤10岁、11～20岁、21～30岁、31～40岁、41～50岁、≥51岁组。分析并比较各组间的血清药物浓度水平及血药浓度在治疗有效范围的患者例数。结果 癫痫患者单一用药多于联合用药,单一服用OXC最多,联合用药VPA最多。血清药物浓度在有效范围内比率最高的是CBZ、低于有效范围下限最多的是LTG、高于有效范围上限最多的是LEV。单一用药组血清LEV水平[7.87(...     

丙戊酸及其与奥卡西平联用治疗儿童癫痫的疗效和安全性比较

目的：考查单用丙戊酸（ VPA）以及VPA与奥卡西平（ OXC）联用治疗儿童癫痫的有效性、安全性和依从性。方法收集2012年10月至2013年10月就诊于中国医科大学附属盛京医院、应用VPA（ VPA组）或VPA联合OXC（ VPA+OXC组）治疗、连续用药2个月以上且随访满1年的癫痫患儿的病历资料进行回顾性分析,记录并比较2组患儿的用药情况[ VPA日剂量、OXC日剂量、VPA标准化血药浓度（ CDR）、用药依从性（以药物保留率评价）]、癫痫控制情况和药物不良反应（ ADR）发生情况。结果共208例患儿纳入研究。VPA组105例,男性62例,女性43例,年龄1~15岁,平均（6.8±3.4）岁;VPA+OXC组103例,男性60例,女性43例,年龄1~15岁,平均（7.4±3.5）岁。VPA 组与 VPA + OXC 组 VPA 日剂量、CDR、药物保留率差异均无统计学意义[（507±207）mg比（498±164）mg,（4.2±2.3）（μg·kg）/（ml·mg）比（4.3±1.6）（μg·kg）/（ml· mg）,81.9%比79.6%,均P>0.05）];随访1年时,VPA+OXC组有效率明显优于VPA组[82.5%（85/103）比61.9%（65/105）,P<0.05）。随访1年期间VPA组与VPA+OXC组ADR症状和肝功能异常发生率差异均无统计学意义[13.3%（14/105）比15.5%（16/103）,4.8%（5/105）比6.8%（7/103）,均P>0.05]。但将患儿按年龄分组比较,则显示1~10岁患儿2组ADR发生率和VPA+OXC组肝功能异常发生率均高于11~15岁患儿（均P<0.05）;按VPA血药浓度分组比较,CDR为5~13（μg·kg）/（ ml·mg）的患儿ADR症状和肝功能异常发生率均高于CDR为1~5（μg·kg）/（ ml·mg）的患儿。结论 OXC与VPA联用治疗儿童癫痫疗效优于单用VAP,同时具有良好的安全性和依从性。患儿年龄和VPA血药浓度可能是发生ADR症状和肝功能异常的危险因素。     

New anti-epileptic drugs for the 21st century

Prior to 1993, there were only six major drugs available in the US for the treatment of patients with epilepsy. These included phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), primidone (PRIM), valproic acid/sodium valproate (VPA) and ethosuximide (ESX). Of these drugs, VPA has the broadest spectrum of activity and ESX the most limited. Despite these six agents, as well as several secondary drugs, it is estimated that over 30% of patients have inadequate seizure control, while others, whose disease is adequately controlled, suffer from bothersome adverse events (AEs). Since 1993, ten new drugs have entered the worldwide market (not all in the US). Those released include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LVT), zonisamide (ZNS), clobazam (CLB) and vigabatrin (VGB). The purpose of this article is to review each of the above drugs, looking at efficacy, safety, tolerability and where they may play a role in the current treatment of epilepsy.     

New anti-epileptic drugs for the 21st century

Prior to 1993, there were only six major drugs available in the US for the treatment of patients with epilepsy. These included phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), primidone (PRIM), valproic acid/sodium valproate (VPA) and ethosuximide (ESX). Of these drugs, VPA has the broadest spectrum of activity and ESX the most limited. Despite these six agents, as well as several secondary drugs, it is estimated that over 30% of patients have inadequate seizure control, while others, whose disease is adequately controlled, suffer from bothersome adverse events (AEs). Since 1993, ten new drugs have entered the worldwide market (not all in the US). Those released include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LVT), zonisamide (ZNS), clobazam (CLB) and vigabatrin (VGB). The purpose of this article is to review each of the above drugs, looking at efficacy, safety, tolerability and where they may play a role in the current treatment of epilepsy.     

Isobolographic characterization of interactions of retigabine with carbamazepine, lamotrigine, and valproate in the mouse maximal electroshock-induced seizure model

The aim of this study was to characterize the pharmacodynamic, pharmacokinetic, and adverse-effect profiles of retigabine (RTG) in combination with carbamazepine (CBZ), lamotrigine (LTG), and valproate (VPA). The isobolographic analysis for parallel and nonparallel dose–response effects was used in the mouse maximal electroshock seizure (MES) model for evaluation of pharmacodynamic interaction. Potential adverse-effect profiles of interactions of RTG with CBZ, LTG, and VPA at the fixed ratio of 1:1 in the MES test were evaluated in the chimney (motor performance), passive avoidance (long-term memory), and grip strength (muscular strength) tests. Free plasma and total brain concentrations of CBZ, LTG, and VPA were determined by immunofluorescence and chromatography to assess pharmacokinetic interaction. In the MES model, RTG administered singly had its dose–response relationship curve (DRRC) parallel to that for VPA and nonparallel to that for CBZ and LTG. With isobolography for parallel DRRCs, the combination of RTG with VPA at fixed ratios of 1:3, 1:1, and 3:1 exerted supraadditive (synergistic) interaction. Isobolography for nonparallel DRRCs revealed that the combinations of RTG with CBZ and LTG at the fixed ratio of 1:1 produced additive interaction. In all combinations, neither motor coordination, long-term memory, nor muscular strength were affected. Only the combination of RTG with VPA at the fixed ratio of 3:1 was complicated by a pharmacokinetic increase in both free plasma and total brain VPA concentrations. All remaining combinations of RTG with VPA, CBZ, and LTG were pharmacodynamic in nature. RTG synergistically interacted with VPA and exerted additive interaction with CBZ and LTG in the mouse MES model.     

Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK).We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3 mM, for 24 h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK.These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent.     

Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta‐analyses

Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta‐analyses using a Bayesian random‐effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs—levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate—should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults.     

左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的Meta分析

目的：评价左乙拉西坦治疗妊娠期癫痫的疗效及其对胎儿的影响。方法：计算机检索Medline、Cochrane library、EMbase、CNKI、万方、维普、CBM数据库,收集有关左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的队列研究和病例对照研究。依据纽卡斯-渥太华量表（NOS量表）对符合纳入标准的临床研究进行质量评价,并采用RevMan5.3进行Meta分析。结果：本研究共纳入11篇队列研究进行分析,采用NOS评分评估偏移风险,其中10项研究的得分均在7~9分。Meta分析结果显示,在妊娠期癫痫发作控制率方面,左乙拉西坦组低于丙戊酸钠组,差异有统计学意义（P<0.05）;而左乙拉西坦与拉莫三嗪、托吡酯、卡马西平或苯妥因单药治疗相比,两组间差异均无统计学意义（P>0.05）。在新生儿严重先天畸形发生率方面,左乙拉西坦组低于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平或苯巴比妥组,差异均有统计学意义（P<0.05）;左乙拉西坦组与奥卡西平组相比,两组间差异无统计学意义（P>0.05）;左乙拉西坦单药治疗组明显低于多药治疗组（P<0.05）。左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别（P>0.05）。结论：妊娠期癫痫患者服用左乙拉西坦单药治疗,其癫痫控制率可能低于丙戊酸钠,但与拉莫三嗪、托吡酯、卡马西平及苯妥因单药治疗疗效大致相当。在胎儿安全性结局方面,左乙拉西坦致畸性可能优于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平及苯巴比妥,合并使用其他抗癫痫药物增加其致畸风险;左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别。本文纳入研究均为队列研究,易受偏移风险的影响,故存在一定局限性。     

Pharmacokinetics of mood stabilizers and new anticonvulsants

Mechanisms of action, efficacy spectra, pharmacokinetics, and adverse effects differentiate the mood stabilizers lithium, carbamazepine (CBZ), and valproate (VPA). Lithium, which has a low therapeutic index, is excreted through the kidneys, resulting in renally mediated, but not hepatically mediated, drug-drug interactions. CBZ also has a low therapeutic index and is metabolized primarily by a single isoform (CYP3A3/4). It has an active epoxide metabolite, is susceptible to CYP3A3/4 or epoxide hydrolase inhibitors, and is able to induce drug metabolism (both via cytochrome P450 oxidation and conjugation). CBZ thus has multiple problematic drug-drug interactions. In contrast, VPA has less prominent neurotoxicity and three principal metabolic pathways, and it is less susceptible to pharmacokinetic drug interactions. Still, VPA can increase plasma concentrations of some drugs by inhibiting metabolism and can increase the free fractions of certain medications by displacing them from plasma proteins. The newer anticonvulsants lamotrigine, topiramate, and tiagabine have different, generally less problematic, hepatically mediated drug-drug interactions. Gabapentin, which is renally excreted, lacks hepatic drug-drug interactions, though bioavailability may be reduced at higher doses. Recently approved anticonvulsants, including oxcarbazepine, zonisamide, and levetiracetam, may have improved pharmacokinetic profiles compared to older agents. Novel psychotropic effects of these drugs may also be demonstrated, based on their mechanisms of action and preliminary clinical data.     

Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study

The aim of this retrospective study was to investigate the influence of oxcarbazepine (OCBZ) and methsuximide (MSM) on lamotrigine (LTG) serum concentrations. The effect of OCBZ compared to carbamazepine (CBZ) and the effect of MSM on LTG serum concentrations were examined in patients with and without valproic acid (VPA) comedication. Altogether, 376 samples from 222 patients were analyzed in routine drug monitoring. Two or more serum samples from the same patient were considered only if the comedication had been changed. For statistical evaluation, regression analytical methods and an analysis of variance were performed. For the analysis of variance, the LTG serum concentration in relation to LTG dose/ body weight--level-to-dose ratio (LDR), in (microg/mL)/(mg/kg)--was calculated and compared for different drug combinations. The nonlinear regression analysis including the LTG dose per body weight, age, gender, and the different kinds of comedication revealed that these variables have a significant influence on LTG serum concentration (r2 = 0.724). The relationship between LTG dose/body weight and serum concentration deviates only slightly from linearity, the LTG concentration was about 18% lower in women than in men, and age had a significant influence. The data indicate that children have significantly lower LTG concentrations than adults on a comparable LTG dose per body weight and that children may be more prone to enzyme induction by comedicated drugs. Methsuximide has a strong inducing effect on the LTG metabolism and decreases the LTG concentrations markedly (about 70% compared to LTG monotherapy). Carbamazepine also reduces the LTG concentrations considerably (by 54%). The inducing effect of OCBZ (29%) was less pronounced but also significant. The inducing effect of MSM, CBZ, and OCBZ was also seen in combination with VPA: VPA alone increases the LTG concentration approximately 211%, whereas in addition to MSM (8%), CBZ (21%), or OCBZ (111%), the increase of LTG was significantly smaller. The analysis of variance confirmed the results of the regression analysis. The effect of MSM on the LTG concentration should be considered if MSM is added or withdrawn in patients treated with LTG. Oxcarbazepine had a less pronounced inducing effect on LTG metabolism compared to CBZ. If CBZ is replaced by OCBZ as comedication, an increase in LTG serum concentrations should be expected.