Which drug for the adult epileptic patient: phenytoin or valproate?

A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered.     

Carbamazepine drug interactions: the influence of concurrent drug therapy on serum concentrations of carbamazepine and its epoxide metabolite

The influence of concurrent drug therapy (phenytoin, valproate, phenobarbital, primidone) on serum concentrations of total and free carbamazepine (CBZ) and its active metabolite carbamazepine-10, 11-epoxide (CBZ-E) in 135 epileptic patients was studied. Serum CBZ and CBZ-E levels were analyzed by high performance liquid chromatography, whereas serum levels of the anticonvulsants were determined by fluorescence polarization immunoassay. Ultrafiltration was used to separate the free drugs from the protein-bound drugs in serum. Patients were divided into five groups according to the medication they received. Linear regression analyses revealed that concurrent drug therapy affected the metabolic rate of CBZ and CBZ-E in various ways. In patients on CBZ monotherapy, 78.3% of CBZ and 52.4% of CBZ-E were bound to plasma proteins. The total serum CBZ and CBZ-E concentrations significantly correlated with their respective free levels in serum. Compared with the CBZ monotherapy group, patients receiving concurrent drug therapy showed higher CBZ clearance and had elevated CBZ-E/CBZ ratios. Although the decrease in the total CBZ concentration depended on the simultaneous phenytoin and valproate concentrations (p less than 0.05), the serum levels of phenobarbital and primidone appeared to have no significant influence on the CBZ concentration. Since great interindividual variations were found in the serum concentration after a given dose, routine monitoring of the CBZ and CBZ-E serum concentrations is essential in designing a safe and effective therapeutic regimen for epileptic patients, especially for those on polytherapy.     

An audit of therapeutic drug monitoring of anticonvulsants.

An audit of therapeutic drug monitoring (TDM) of anticonvulsants was performed to assess both its use and misuse in the management of patients with epilepsy. Over a four week period all samples received for phenytoin, carbamazepine, sodium valproate and phenobarbitone assays were included in the audit. The aims were to establish the source of the specimens, the reasons for the requests and to ascertain what action, if any, would be taken when the result of the assay was provided. A total of 163 separate assays were performed over the four week period (43 phenytoin, 74 carbamazepine, 41 valproate, 5 phenobarbitone). Only 18.7% of all requests originated from the adult neurology department. The vast majority of tests had been ordered by junior medical staff (only 10% by consultants) and approximately 50% were 'routine' with no satisfactory clinical reason for the request offered. There was a tendency to manipulate prescribed doses on the basis of drug levels alone without taking the clinical picture into consideration. These results demonstrate a general ignorance, especially amongst junior medical staff, of the value of TDM of anticonvulsants, and reinforce the need for both an educative and interpretive service to be provided by the Chemical Pathology Department.     

1例丙戊酸钠治疗癫痫持续状态引起高血氨脑病的病例分析

丙戊酸钠是一种临床广泛使用的抗癫痫药物，用于癫痫患者的全身性和部分性发作。然而，其不良反应多，如高血氨症、肝毒性、内分泌紊乱等。对于接受大剂量或长期使用丙戊酸钠治疗的患者来说，高血氨症最为常见，其可引起中枢神经系统损害，包括严重的高血氨脑病。这样势必会影响丙戊酸钠的临床应用。本文通过对1例丙戊酸钠治疗癫痫持续状态引起高血氨脑病的病例进行分析及合理干预，希望为临床合理使用抗癫痫药物提供一定的参考，避免不良反应的发生，提高药物治疗效果。     

血液与唾液中苯巴比妥浓度之间相关性的研究

目的:用HPLC法测定癫痫患者血液与唾液中苯巴比妥的浓度,对两者之间的相关性进行研究,考查是否可以在临床药物监测中用唾液代替血液作为检测样本。方法:测定癫痫患者血液与唾液中苯巴比妥的浓度,采用数理统计的方法对两者之间的相关性进行研究。结果:血液与唾液中苯巴比妥浓度之间具有良好的相关性.结论:在临床药物监测中,可以用唾液代替血液作为检测样本。     

丙戊酸镁和丙戊酸钠治疗癫痫部分性发作的单盲交叉试验

本文采用单盲交叉法,比较了丙戊酸镁和丙戊酸钠治疗癫痫部分性发作的临床疗效。结果显示丙戊酸镁的显效率明显高于丙戊酸钠(P<0.05),但两药平均每月发作频率和总有效率无显著差别(P<0.05)。近期脑电图监测未能反映临床控制程度,丙戊酸镁治疗前后的血镁浓度几乎无改变,在治疗剂量范围内未发现严重的毒副反应。     

奥卡西平和丙戊酸钠对癫痫患者血浆同型半胱氨酸和不对称二甲基精氨酸水平的影响

目的：探讨奥卡西平（OXC）和丙戊酸钠（VPA）对癫痫患者血浆同型半胱氨酸（Hcy）和不对称二甲基精氨酸（AD-MA）水平的影响。方法分别检测 OXC 组32例和 VPA 组36例单药治疗的癫痫患者血浆 Hcy 和 ADMA 水平,与对照组比较,并分析 Hcy 和 ADMA 水平与抗癫痫药物治疗时间的相关性。结果 OXC 组和 VPA 组患者血 Hcy、ADMA 水平高于对照组（P ＜0．05）,OXC 组和 VPA 组比较,差异无统计学意义（P ＞0．05）;抗癫痫药治疗时间与血浆 Hcy、ADMA 水平均呈正相关（r ＝0．274、0．256,P ＜0．05）。结论 OXC 和 VPA 可引起癫痫患者血浆 Hcy、ADMA 水平升高,长期服用 OXC 和 VPA 的癫痫患者应监测血 Hcy、ADMA,及时补充 B 族维生素、叶酸有利于减少血栓事件的发生。     

抗癫痫药物与血脂异常相关性的Meta分析

目的 运用Meta分析方法评估抗癫痫药物与血脂异常的相关性,为合理选择抗癫痫药物及明确抗癫痫药物对血脂异常的不良影响提供更为有利的依据.方法 以"抗癫痫药"、抗惊厥药"及"血脂"为关键词对万方、维普及中国知网三大数据库建库至2017年3月所有文献进行检索.仅纳入关于抗癫痫药物与血脂异常的病例对照研究及队列研究.对所纳入的文献进行客观的评价质量后,采用RevMan5.3分析软件进行数据分析.结果 最终纳入18篇研究,共878例研究对象,涉及到的抗癫痫药物包括丙戊酸钠、卡马西平、苯妥英钠、苯巴比妥、拉莫三嗪及托吡酯.Meta分析结果示丙戊酸钠会导致总胆固醇(TC)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)水平的增加,差异具有显著统计学意义(P<0.01);卡马西平会增加TC、甘油三酯(TG)、HDL-C及LDL-C的水平,差异有显著统计学意义(P<0.01).苯妥英钠会降低TC、TG及LDL-C的血清水平,差异具有显著统计学意义(P<0.01).结论 抗癫痫药可能会改变癫痫患者血脂水平,尤其是卡马西平、丙戊酸钠及苯妥英钠.临床医生及癫痫患者都需提高对血脂异常的管理,从而避免血管疾病的发生.     

Salivary theophylline estimation in the management of asthma in children.

Simultaneous sampling was performed to determine whether saliva could replace plasma in the monitoring of theophylline dosages. Forty-eight children with moderate to severe asthma received oral theophylline preparation (usually sustained release) on a daily basis. They provided simultaneous saliva and plasma samples at routine out-patient visits. Saliva and plasma theophylline concentrations showed a wide variation between individuals, and their ratios also differed. Saliva theophylline concentrations below 7 micrograms/ml reflect plasma concentrations below 10 micrograms/ml, i.e. sub-therapeutic, while saliva concentrations above 7 micrograms/ml are consistent with therapeutic dosage. Estimation of saliva theophylline concentration on routine visits avoids the discomfort of blood sampling. It reflects whether daily oral theophylline dosage in childhood asthma is below or within the therapeutic range. The need for changes in dosage and the degree of patient-compliance with therapy can be usefully indicated.     

苯妥因钠、丙戊酸钠、卡马西平对癫痫患者智力的影响

抗癫痫药物造成认知功能的损害及损害程度迄今仍无明确结论。为此，我们对46例全面性强直一阵挛发作的癫痫患儿进行了服药前后的智力测验，并以16例健康同龄人对照，以检测苯妥因钠、丙戊酸钠、卡马西平对智力的影响。结果表明：服药3－4个月后，在血药浓度水平于治疗范围内的情况下，苯妥因钠组病人的操作智商，知觉组织智高较对照组低（P＜0．05），而丙戊酸钠组及卡马西平组相互比较并与对照组比较则元显著差异。提示苯妥因销影响患儿的记忆、注意、抽象思维能力、空间知觉能力及学习能力，而丙戊酸钠及卡马西平对智力则无明显影响。     

Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study

Patients who use phenytoin and some other anticonvulsive drugs have been shown to have raised concentrations of plasma high density lipoprotein. As this lipoprotein is known to be inversely associated with the incidence of ischaemic heart disease the causes of death of all patients with epilepsy known to be taking anticonvulsive drugs who died during 1978-80 were studied. Of 1399 deaths of anticonvulsant users, 258 (18.4%) were caused by ischaemic heart disease. This was significantly less (p less than 0.001) than the 382 deaths from ischaemic heart disease (27.3%) observed among paired controls matched for sex, age, and date of death. The total cardiovascular mortality was also lower among patients with epilepsy than among controls (p less than 0.02) despite there being more deaths due to cerebrovascular disease among patients. The difference in mortality from ischaemic heart disease was significant for both sexes and was not accounted for by excess deaths due to any other single cause. Users of phenytoin, carbamazepine, and barbiturates (alone or in combination) showed 29% less mortality due to ischaemic heart disease than respective controls (p less than 0.001).     

Removal of phenytoin by hemodialysis in uremic patients

The removal of phenytoin by hemodialysis was determined in seven uremic patients. Four patients were receiving phenytoin sodium for therapeutic purposes; three received one dose each intravenously to quantitate its disposition in uremia. The drug was measured in whole blood, plasma, saliva, and dialysate. Only 2% to 4% of the intravenous dose was recovered in the dialysate. Phenytoin clearance by dialysis was 7 to 14 ml/min; plasma clearance was 53 to 133 ml/min. Since hemodialysis contributes little toward shortening to 11-to-18-hour half-life of phenytoin in the uremic patients, no supplemental dose is necessary for uremic patients undergoing hemodialysis.     

儿童苯妥因群体药动学研究

目的 :研究儿童苯妥因的群体药动学。方法 :收集 4 2例门诊患儿的常规治疗药物监测数据 ,应用自编程序 Monte Carlo法提取儿童苯妥因群体药动学参数和个体药动学参数。结果 :儿童苯妥因群体药动学参数 Vm和Km分别为单独用药组 9.8mg· kg-1· d-1和 2 .73mg/ L,合并用药组 9.2 mg·kg-1·d-1和 3.2 4 mg/ L;预测血药浓度与实测浓度显著相关 (r分别为 0 .999和 0 .984 ,P<0 .0 1)。结论 :合用苯巴比妥或氯硝安定对苯妥因的药动学有显著影响。本研究为儿童苯妥因给药方案个体化提供有价值的依据。     

唾液与血清肾功能检测指标的相关性

目的 通过检测唾液与血清中肾功能指标的相应数据，从中探讨其相关性，为临床提供一条肾功能检查的新逢径，方法 对54例患者于同日清晨采集唾液与血清并同步进行UN，CRE，HCO3^-，K^＋，GLU检测，然后进行唾液与血清检测指标的相关性分析，并进行统计学处理。结果 唾液与血清UN，CRE有显著相关性（r=0．957，P〈0．01；r=0．929，P〈0．01）．HCO3^-，K^＋，GLU无相关性（P〉0．05）．结论 唾液中UN,CRE的检测数据可以作为评价肾功能的指标应用于临床。     

尿苷二磷酸葡萄糖醛酸转移酶1A6基因多态性对丙戊酸钠代谢的影响

目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A6（UGT1A6）基因多态性对丙戊酸钠血药浓度的影响。方法选择单药服用丙戊酸钠且无肝肾功能异常的癫痫患者67例,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析患者的UGT1A6基因552位点的多态性;同时应用荧光偏振免疫法（FPIA）测定患者丙戊酸钠的血药浓度。结果67例患者中UGT1A6的552位点基因型为A／A,A／C及C／C的例数分别40（59．7％）、24（35．8％）及3（4．5％）。A／A组标准血药浓度均值（4．32±0．21）μg·kg·ml^-1·mg^-1和A／C组（3．43±0．30）μg·kg·ml^-1·mg^-1比较差异有统计学意义;含有C等位基因的A／C及C／C作为一组[标准血药浓度均值（3．40±0．28）μg·kg·ml^-1·ng^-1]与A／A组比较,其标准血药浓度均值差异具有统计学意义。结论UGT1A6是丙戊酸钠的代谢酶,UGT1A6基因多态性可影响丙戊酸钠的代谢,UGT1A6基因552位点含有C等位基因的患者应用丙戊酸钠应较常规增加用药剂量。     

胶束电动毛细管色谱法和荧光偏振免疫法测定癫痫患者血浆中苯妥英浓度的比较

目的:比较治疗药物监测中胶束电动毛细管色谱法(MECC)和荧光偏正免疫法(FPIA)测定血浆中苯妥英的浓度。方法:收集该院31例服用苯妥英的癫痫患者稳态浓度的血浆样品,分别以MECC和FPIA进行测定,用回归法考察两种方法测定结果的相关性。结果:两种方法无显著差异,具有良好的相关性(P>0.05)。回归分析的线性方程YFPIA=1.044×XMECC,相关性分析r=0.967。结论:MECC法可在无TDx仪的情况下替代FPIA,而且成本较低,快速简便。适用于苯妥英单用,以及苯妥英与常用抗癫痫药物(卡马西平、扑米酮、丙戊酸、苯巴比妥、氯硝西泮)合用的临床监测。     

The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic

To assess the most efficient means of monitoring thyroid status in an epilepsy clinic, total thyroxine (T4), free thyroxine stimulating hormone (TSH) were measured in 71 adult patients treated long-term with either phenytoin (DPH), carbamazepine (CBZ) or sodium valproate (VAL). Twenty-seven patients with one or more abnormal thyroid hormone results were further investigated by a thyrotrophin releasing hormone (TRH) test and clinical assessment. T4 was found to be normal in 85% on VAL, 40% on CBZ and 39% on DPH. FT4 was normal in more patients, namely 95% on VAL, 70% on CBZ and 65% on DPH. The TRH tests indicated that FT4 was the most efficient screening test for hypothyroidism in this epileptic population. We estimate that the use of FT4 alone as a screening test would have reduced by 60% the number of TRH tests required.     

Plasma level monitoring of oxcarbazepine in epileptic patients

BACKGROUND: Despite the wide use of oxcarbazepine (OXC) there is little data concerning the usefulness of plasma level monitoring with this drug in Mexican patients with epilepsy. The purpose of the present study was to determine whether OXC levels correlate with dose, age, weight, or drugs used concomitantly. METHODS: Plasma levels of the antiepileptic drug OXC were evaluated in 214 patients with epilepsy. In each patient, plasma MHD (10-hydroxycarbazepine, the main metabolite of OXC) concentration was determined. Additionally, plasma protein binding was determined in 30 patients and affinity to red blood cells (RBCs) was evaluated in 50 patients. RESULTS: Our results showed that the mean plasma level of MHD was 15.34 microg/mL, mean protein binding ranged between 30-40%, and the mean RBC concentration was 18.38 microg/mL. A relationship between dose/weight and plasma concentration was found (r = 0.5149, p <0.001). In addition, a linear relationship between plasma and RBC concentration was established (r = 0.8806, p <0.0001). CONCLUSIONS: These results suggest that for OXC, routine RBC concentrations are not necessary to make drug adjustments.     

丙戊酸钠血药浓度与抗癫痫疗效及影响因素分析

目的：研究丙戊酸钠血药浓度与抗癫痫疗效及影响因素的关系,为临床个体化用药指导提供依据。方法对重庆医科大学附属永川医院133例服用丙戊酸钠的患者进行血药浓度测定,对血药浓度监测结果进行统计分析,并对133例患者抗癫痫疗效进行观察及分析。结果80例患者癫痫得到了控制,占60．15％,有效血药浓度（50～100 m g／L ）范围内有51例患者癫痫得到控制,占38．35％。血药浓度小于50 m g／L的44例患者中,26例未得到控制;男性与女性的血药浓度分布相似;丙戊酸钠血药浓度在各年龄组之间存在差异,成年组有52．87％患者血药浓度低于或高于治疗范围,未成年组则有39．13％;随着血药浓度增加,不良反应增加。结论丙戊酸钠的血药浓度与患者抗癫痫疗效之间存在个体差异,临床应用时,应根据患者的丙戊酸钠血药浓度、癫痫控制情况及年龄进行合理的个体化给药。     

托吡酯与丙戊酸钠治疗小儿癫痫的有效性及安全性对照研究

目的评估托吡酯与丙戊酸钠在治疗小儿癫痫的疗效及安全性的差异。方法54名癫痫患儿随机分为托吡酯治疗组（n=30）与丙戊酸钠治疗组（n=24）。托吡酯治疗组接受托吡酯治疗,剂量从每晚1次1—3mg·kg-1·d-1（最大：25mg）增加到5-9mg·kg-1·d-1,分2次;丙戊酸钠治疗组接受丙戊酸钠20mg／kg（分2次）,逐渐加量,严重病例在检测血药浓度情况下,可加量至最高40mg／kgo记录住院期间的可能副作用。结果两组总有效率分别为70％、667％％,差异不具有统计学意义（P=0．793）;不良反应发生率分别为26．67％和16．67％,差异不具有统计学意义（P=0．583）。结论治疗小儿癫痫,托吡酯与丙戊酸钠的有效性及安全性不存在明显差异。