86例儿童抗癫痫药物的血药浓度监测和疗效分析

本文用荧光偏振免疫法(FTIA)和稳态血药浓度一点法对监测86例癫痛患儿血药浓度并进行疗效分析。结论：单用一药能控制症状者不宜并用两药；单一型患者服一种药物较理想；癫痫大发作婴幼儿宜用苯巴比妥不宜用苯妥英钠；癫痫患儿其抗瘢痫药物的血药浓度控制至关重要，应加强血药浓度监测。     

服用"纯中药"制剂的癫痫患者抗癫痫药血药浓度监测

目的:了解某些抗癫痫"纯中药"制剂中是否含有抗癫痫西药成分,为临床合理用药提供依据.方法:对服用"纯中药"制剂的30例癫痫患者,用荧光偏振免疫法(FPIA)筛检其是否含有丙戊酸(VPA)、卡马西平(CBZ)、苯巴比妥(PB)、苯妥英钠(DPA)等4种常用抗癫痫西药.结果:30例患者中,检测出上述1～4种常用抗癫痫西药的28例,d;93.3%.其中VPA16例,平均浓度(12.02±14.97)μg·ml-1;CBZ 20例,平均浓度(2.43±2.54)μg·ml-1;PB 23例,平均浓度(14.57 ±16.63)μg·ml-1;DPA 22例,平均浓度(7.31±13.43)μg·ml-1.结论:在所谓的抗癫痫"纯中药"制剂中暗加西药较普遍,严重侵犯了患者知情权,妨碍了抗癫痫的正规治疗,有损患者健康.     

抗癫痫中药制剂服用者抗癫痫西药血药浓度检测

目的：解并证实某些抗癫痫纯中药制剂中是否会有抗癫痫类西药成份，以便为临床安全，合理用药提供理论与实验依据。材料与方法，对已服用各种（共22种）抗癫痫中药制剂的42例癫痫患者，用荧光偏振免疫法（FPIA）监测苯妥英，丙戊酸，卡马西平，苯巴比妥4种抗癫痫药物的血药浓度。结果：22种抗癫痫中药制剂中不同程度的含有1－4种抗癫痫类西药；单服中药的25例患者，20例癫痫症状者得不到控制，5例引起中毒；中药与西药联合中药17例中，2例引起中毒。结论：服用某些抗癫痫中药的患者，必须监测其中所含西药成份的血药浓度，建议生产这些含西药的抗癫痫中药制剂时，应标明所含西药成份及含量，以便医生合理用药，最好是不加入抗癫痫类西药成分，以免疫加入西药的剂量不足而达不到治疗目的。或因加入的西药成份剂量过大而引发起中毒；中西药联合用药时，应考虑所服中药中含有抗成份之间的相互作用和联用药的相互作用。     

视频脑电图监测对发作性疾病的诊断价值

目的：探讨视频脑电图(VEEG)对发作性疾病的诊断价值。方法：对62例发作性疾病患者进行VEEG监测，并与普通脑电图(REEG)进行对比分析。结果：REEG正常47例(75．8％)，异常15例(24．2％)，其中痫样放电13例(21．0％)，临床发作1例(1．6％)。而VEEG监测正常20例(32.3％)，异常42例(67．7％)，其中痫样放电38例(61．3％)，监测到临床发作22例(35．5％)。最终诊断癫痫性发作38例，非癫痫性发作24例。结论：VEEG监测对癫痫发作及非癫痫发作的诊断和鉴别有重要价值。     

通过TDM分析3例抗癫痫药合并"中成药"中毒

有些不法药商打着“副作用少，易停药的特效纯中药制剂治疗癫痫”的幌子，欺骗患者，其实是在配方中加入一些化学抗癫痫药，如服用不当．易引起中毒反应。本文通过TDM分析3例抗癫痫药合并“中成药”中毒情况，以引起临床注意。     

视频脑电图在新生儿癫痫发作中的应用效果研究

目的探究视频脑电图(VEEG)在新生儿癫痫发作中的应用效果。方法选择2016年7月～2017年11月我院小儿内科50例新生儿惊厥发作患儿,均进行VEEG监测,并分析其检查结果。结果 (1)50例新生儿中,15例患儿临床发作与痫样放电同步出现,可诊断为癫痫发作;另有7例患儿为发作期无同步痫样放电,诊断为非癫痫发作。(2)15例癫痫发作患儿结合病史、临床症状以及VEGG表现可明确其癫痫发作类型,分别为2例局部强直性发作,2例肌阵挛性发作,11例局部阵挛性发作。(3)33例患儿通过VEEG监测到痫样放电,其中睡眠期痫样放电频率63.64%,显著高于清醒期27.27%;(4)33例痫样放电患儿其起源部位多为局灶放电87.88%,且主要以颞区为主。另外,通过探讨痫样放电检出率与病因关系发现,脑器质性病变痫样放电异常率最高75.76%。(5)治疗后3个月随访发现,微小型、单灶阵挛发作患儿其预后90.63%要好于其他惊厥发作类型的患儿,且惊厥性发作持续时间在48h以上、发作次数≥3次的患儿其后遗症发生几率更高,差异有统计学意义(P<0.05)。结论在新生儿惊厥发作诊治中,应用VEEG不仅能够提高癫痫的临床诊断及分型的准确率,有效鉴别非癫痫发作性疾病,还可用于早期新生儿癫痫发作预后判断的一种有效检查手段。     

服抗癫痫中药55例血药浓度监测与安全用药

目的：监测服用抗癫痫中药制剂癫痫患者的血药浓度，鉴别其中的西药成分，配合临床安全合理的使用药物，确保患者用药安全。方法：采用荧光偏振免疫分析法测定55名癫痫患者所服用的抗癫痫“纯中药”制剂中苯巴比妥、苯妥英、丙戊酸和卡马西平的血药浓度。结果：55例患者所服用的32种中药制剂中有6种未检出任何化学成分，其他服用中药制剂的癫痫患者的血液样本中都不同程度的检出抗癫痫化学成分，有的还多达3种。结论：中药制剂厂家在药品说明书中应注明中西药成分，保障患者用药安全；药师应做好癫痫患者用药教育，合理应用抗癫痫药物。     

小儿抗痫胶囊联合丙戊酸钠治疗儿童原发性全身强直–阵挛发作型癫痫的临床研究及其对GFAP、S100β水平的影响

目的探究小儿抗痫胶囊联合丙戊酸钠缓释片(I)治疗儿童原发性全身强直–阵挛发作型癫痫的临床疗效及其对胶质纤维酸性蛋白(GFAP)、S100β蛋白水平的影响。方法选取2018年2月—2020年2月在开封市儿童医院就诊的120例原发性全身强直–阵挛发作型癫痫患儿为研究对象,按照随机数字表法将全部患儿分为对照组和治疗组,每组各60例。对照组患儿口服丙戊酸钠缓释片(I),30mg/(kg?d)。治疗组在对照组用药基础上口服小儿抗痫胶囊,5粒/次,3次/d。2个月为1个疗程,两组患儿均连续治疗3个疗程。观察两组患儿的临床疗效,并比较两组患儿治疗前后脑电图特征、癫痫发作持续时间、癫痫发作频率、GFAP、S100β蛋白水平情况。结果治疗后,治疗组总有效率(93.33%)明显高于对照组(80.00%)(P0.05)。治疗后,两组患儿θ功率均较治疗前增加(P0.05),且治疗组θ功率显著高于对照组(P0.05)。治疗后,两组患儿癫痫发作持续时间、发作频率均明显降低(P0.05);且与对照组比较,治疗组癫痫发作持续时间、发作频率明显降低(P0.05)。治疗后,两组GFAP、S100β水平均降低(P0.05),且治疗组GFAP、S100β水平较对照组低(P0.05)。结论小儿抗痫胶囊联合丙戊酸钠缓释片(I)治疗儿童原发性全身强直–阵挛发作型癫痫疗效显著,能够有效改善患儿临床症状、脑电图特征、θ功率和GFAP、S100β水平,且不会增加不良反应。     

癫痫患者2种治疗药物浓度的监测及其临床意义

目的：监测治疗癫痫患者血清中苯妥英（ＰＨＴ）和卡马西平（ＣＢＺ）的浓度。方法：建立高效液相色谱法,测定住院和门诊７８例癫痫患者血药浓度。结果：其中服用苯妥英２３例,卡马西平５５例,低于治疗有效浓度分别有１４例和１９例,各占６０．８７％和３４．５５％,中毒浓度１例。结论：癫痫患者的治疗与苯妥英和卡马西平的用药水平有关,治疗剂量不能仅凭经验用药,有条件则应进行血药浓度监测,实行个体化给药。     

自拟"止痫散"治疗小儿癫痫12例

目的:总结自拟“止痫散”治疗小儿癫痫的疗效。方法:12例患儿均长期服用“止痫散”,重者2～3次/d,轻者1～2次/d,温开水送服。间断配合汤剂,并随症加减。结果:基本治愈5例,明显好转5例,无效2例,总有效率为83.3%。结论:运用“止痫散”辨证治疗小儿癫痫疗效满意,并在治疗过程中可停服西药。     

抗癫痫“中药”中西药成分的血药浓度监测及疗效分析

目的:对单用"中药"治疗的癫痫患者西药成分的血药浓度进行监测并评估其疗效。方法:对1997年2月～2006年6月在我院就诊及监测血药浓度的60例癫痫患者,于监测期间仅服用"中药"进行抗癫痫治疗后,用荧光偏振免疫分析法测定4种西药的血药浓度。结果:60例患者中,丙戊酸、卡马西平、苯妥英、苯巴比妥分别被检出18、40、41、47例/次,平均每例患者被检出含2种以上西药,绝大多数血药浓度处于有效范围以外,且总体疗效差。结论:在"中药"中检出的西药成分组方不符合癫痫的药物治疗原则,临床应谨慎对待这类抗癫痫"中药"。     

癫痫的药物治疗研究进展

抗癫痫药物治疗是癫痫临床治疗的主要方案,目前临床治疗中尚存在诸多问题。本文综述近年遗传学研究对癫痫治疗的影响、治疗药物监测、中药治疗机制以及新型抗癫痫药物开发等研究进展。     

Pharmacokinetic, pharmacodynamic, and pharmacogenetic targeted therapy of antiepileptic drugs

Therapeutic drug monitoring (TDM) is widely accepted as a method to improve the effectiveness and safety of the first generation antiepileptic drugs (AEDs) and to identify an individual's optimum concentration. Like the older AEDs, the new AEDs also have significant pharmacokinetic variability. A similar relationship between concentration and effect for the new and old AEDs in experimental seizure models suggests that it is reasonable to use TDM for the new AEDs. With the addition of generic formulations of the new AEDs, TDM can play an important role to validate bioequivalence in patients. There is a history of problems with generics of the older AEDs, primarily carbamazepine and phenytoin. The Biopharmaceutics Classification System, which correlates the solubility and permeability of a drug with oral drug absorption, predicts that there should be no significant problems with the majority of the new AEDs. Because of the controversy over the risk-benefit of generic substitution of AEDs, the use of TDM will provide a way to ensure patient safety while establishing that generics of AEDs proven to be bioequivalent in population studies are also bioequivalent in individuals. The goal of personalized medicine is to use genetic testing to target therapy and identify those individuals unlikely to respond to a drug or likely to respond adversely to the same drug. Of all the AEDs, only phenytoin undergoes significant metabolism by cytochrome P450 isozymes with significant genetic polymorphisms (CYP2C9, CYP2C19). Studies are still needed to identify genetic and biomarkers to identify patients at risk for serious idiosyncratic reactions. There have been significant advances in the understanding of the role of genetics in idiopathic as well as acquired epilepsies. Identification of experimental and clinical evidence linking functional changes associated with gene mutations to epilepsy syndromes will help provide new molecular targets for future AEDs.     

Can pharmacokinetic variability be controlled for the patient's benefit? The place of TDM for new AEDs

The aim of this brief communication is to update our recent review on therapeutic drug monitoring (TDM) of the newer antiepileptic drugs (AEDs). The potential value of TDM is discussed in relation to their mode of action and their pharmacokinetic proper-ties. Data on the relationships between serum concentrations and clinical efficacy are limited, and few studies have been designed primarily to study these relationships. As yet there are no generally accepted target ranges for any of the new AEDs. For most drugs a wide range in serum concentration is associated with clinical efficacy,and there is a considerable overlap in serum concentrations related to toxicity and lack of clinical efficacy. Although the available documentation is clearly insufficient, the pharmacological properties of some of the drugs suggest that they may be suitable candidates for TDM. The primary role of TDM for both the newer and established AEDs is to identify an individual's optimum concentration and thus establish a reference value in that patient.     

Pharmacokinetic variability of newer antiepileptic drugs: when is monitoring needed?

A new generation of antiepileptic drugs (AEDs) has reached the market in recent years with ten new compounds: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, vigabatrin and zonisamide. The newer AEDs in general have more predictable pharmacokinetics than older AEDs such as phenytoin, carbamazepine and valproic acid (valproate sodium), which have a pronounced inter-individual variability in their pharmacokinetics and a narrow therapeutic range. For these older drugs it has been common practice to adjust the dosage to achieve a serum drug concentration within a predefined 'therapeutic range', representing an interval where most patients are expected to show an optimal response. However, such ranges must be interpreted with caution, since many patients are optimally treated when they have serum concentrations below or above the suggested range. It is often said that there is less need for therapeutic drug monitoring (TDM) with the newer AEDs, although this is partially based on the lack of documented correlation between serum concentration and drug effects. Nevertheless, TDM may be useful despite the shortcomings of existing therapeutic ranges, by utilisation of the concept of 'individual reference concentrations' based on intra-individual comparisons of drug serum concentrations. With this concept, TDM may be indicated regardless of the existence or lack of a well-defined therapeutic range.The ten newer AEDs all have different pharmacological properties, and therefore, the usefulness of TDM for these drugs has to be assessed individually. For vigabatrin, a clear relationship between drug concentration and clinical effect cannot be expected because of its unique mode of action. Therefore, TDM of vigabatrin is mainly to check compliance. The mode of action of the other new AEDs would not preclude the applicability of TDM. For the prodrug oxcarbazepine, TDM is also useful, since the active metabolite licarbazepine is measured.For drugs that are eliminated renally completely unchanged (gabapentin, pregabalin and vigabatrin) or mainly unchanged (levetiracetam and topiramate), the pharmacokinetic variability is less pronounced and more predictable. However, the dose-dependent absorption of gabapentin increases its pharmacokinetic variability. Drug interactions can affect topiramate concentrations markedly, and individual factors such as age, pregnancy and renal function will contribute to the pharmacokinetic variability of all renally eliminated AEDs. For those of the newer AEDs that are metabolised (felbamate, lamotrigine, oxcarbazepine, tiagabine and zonisamide), pharmacokinetic variability is just as relevant as for many of the older AEDs. Therefore, TDM is likely to be useful in many clinical settings for the newer AEDs. The purpose of the present review is to discuss individually the potential value of TDM of these newer AEDs, with emphasis on pharmacokinetic variability.     

关注抗癫癎药的联合用药 警惕药物中毒

癫癎药物治疗原则上要求单一用药。然而,癫癎患者常常因症状控制不佳而联合用药。因抗癫癎药之间相互作用导致药动学的改变,增加了安全隐患,甚至出现药物中毒。本文通过分析癫癎患者联合应用苯妥英钠和丙戊酸钠后,前者影响后者的药动学过程而导致药物过量,提醒应关注抗癫癎药的联合使用,警惕因药物相互作用而引起药物中毒,提高合理用药水平。     

Pharmacotherapy for children and adolescents with epilepsy

INTRODUCTION: Childhood epilepsies are the most frequent neurological problems that occur in children. Despite the introduction of new antiepileptic drugs (AEDs) 25-30% of children with epilepsy remain refractory to medical therapy. AREAS COVERED: This review aims to highlight the main published data on the treatment of childhood epilepsy. The electronic database, PubMed, and abstract proceedings were used to identify studies. The aim of antiepileptic therapy should be to provide complete seizure control, if possible without the burden of any side effect. Since 1993, new agents have been approved for use as an antiepileptic. Although there are few published data (especially in pediatric populations) to establish that the second-generation AEDs are more efficacious than the older AEDs, they appear to have better tolerability. EXPERT OPINION: Old AEDs are efficacious agents that continue to play a major role in the current treatment of epilepsy. These agents actually remain the first-line treatment for many specific seizure types or epileptic syndromes. The new AEDs were initially approved as adjunct agents and--subsequently--as monotherapy for various seizure types in the adult and children. Despite these improvements, few AEDs are now considered to be a first-choice for the treatment of epilepsy in children.     

抗癫痫药物在肝肾功能不全患者中使用的研究进展

临床常用抗癫痫药物根据其药动学特点可分为主要经肝代谢、主要经肾排泄和肝肾双通道清除。肝功能不全患者尽量选择主要经肾排泄的抗癫痫药物,如加巴喷丁、普瑞巴林,或评估肝功能不全的程度,适当的减少剂量。肾功能不全的患者尽量选择主要经肝代谢的抗癫痫药物,如丙戊酸钠、卡马西平、拉莫三嗪,或评估患者的肌酐清除率（CLcr）,根据CLcr进行剂量调整。对于透析的患者,结合血药浓度监测透析后补充剂量有助于个体化治疗。肝肾功能不全患者抗癫痫药物的选择、剂量调整应综合考虑患者肝肾功能情况、药物代谢特点、合并疾病、个体耐受性等因素,在抗癫痫药物使用过程中,加强对药物相互作用、药物不良反应等的监护,结合血药浓度监测,以提高临床用药的有效性与安全性。     

抗癫痫中成药中非法添加西药成分的血药浓度监测分析

目的：对长期服用抗癫痫中成药的患者进行血药浓度监测,查明抗癫痫中成药中非法添加的西药成分。方法：通过全自动生化分析仪,采用酶联免疫法测定中成药中添加的丙戊酸、卡马西平、苯巴比妥、苯妥英的种类及血药浓度。结果：所有服用抗癫痫中成药的患者中均检测到上述四种西药成分,其中含丙戊酸17例,血药浓度在有效范围内占23.53%;含卡马西平17例,血药浓度在有效范围内占17.65%;含苯巴比妥17例,血药浓度在有效范围内占41.18%;含苯妥英5例,血药浓度在有效范围内占60.00%。结论：本方法操作简便、准确,可快速筛查抗癫痫中成药中非法添加的西药成分,便于临床指导患者合理用药。     

Evaluation of therapeutic drug monitoring of antiepileptic drugs

Results of the therapeutic drug monitoring (TDM) of the concentration of antiepileptic drugs (AEDs), performed at Aseer Central Hospital over a 1-year period were evaluated. Most of the requests were for phenytoin (PHT) determination followed by carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PB). Serum concentrations of PB, CBZ, VPA and PHT within the presumed therapeutic range constituted 87%, 73%, 45% and 33%, respectively. Valproic acid exhibited age differences in the proportion of concentrations below the presumed therapeutic range, such that subtherapeutic concentrations increased while therapeutic concentrations decreased with age. When the requests were related to particular patients, 71% of patients were on monotherapy with PHT as the most commonly used single drug and PB the least. Patients using 2 AEDs were found to constitute 23.5% of all patients with "PHT + CBZ" and "CBZ + VPA" being the most commonly prescribed 2 drugs combination. The frequency of concentrations within the therapeutic ranges decreased when 1 or 2 more drugs were used with either PHT or VPA. In addition, combination with PHT was associated with a reduction in mean CBZ concentration, while combination with CBZ was associated with a reduction in mean VPA concentration.