拉莫三嗪联合丙戊酸钠治疗外伤性癫癎复发疗效观察

目的 探讨丙戊酸钠治疗外伤性癫癎复发后,比较添加卡马西平或拉莫三嗪联合治疗外伤性癫癎效果.方法　采用开放性试验的方法对131例丙戊酸钠治疗外伤性癫癎复发患者,进行卡马西平或拉莫三嗪联合丙戊酸钠治疗,以治疗前3个月癫癎发作频度为对照,对治疗6个月后的疗效、不良反应及安全性进行自身对比观察.结果　应用卡马西平或拉莫三嗪联合丙戊酸钠治疗6个月后,患者发作频率均较用药前明显减少;发作频率减少≥50％的患者分别为72.6％和91.3％,差异有统计学意义(P＜0.01);卡马西平联合丙戊酸钠不良反应的发生率为37.1％,拉莫三嗪联合丙戊酸钠不良反应的发生率为8.7％.结论　拉莫三嗪联合丙戊酸钠治疗外伤性癫癎复发疗效确切,不良反应轻微.     

1 072例患者抗癫(癎)药血药浓度监测分析

目的 通过对抗癫(癎)药物血药浓度监测结果分析,为临床提高本类药物的治疗水平作参考.方法 采用荧光偏振免疫法对568例服用丙戊酸钠、374例服用卡马西平、85例服用苯妥英钠和45例服用苯巴比妥的患者血药浓度监测结果及临床疗效分析、评价.结果 抗癫(癎)药治疗指数小,安全度较低,其作用的个体差异大.结论 癫(癎)患者应重视血药浓度监测,并结合其他因素调整用药方案,以达到安全、有效、合理应用抗癫(癎)药.     

248例卡马西平血药浓度监测结果分析

目的分析盐城市第三人民医院神经内科2006年8月至2009年8月间248例卡马西平血药浓度监测结果。方法利用HPLC法测定卡马西平血药浓度,并结合临床疗效、年龄、性别、合并用药情况进行分析。结果 168例患者卡马西平的血药浓度维持4～12μg/mL,其中152例有效(90.5%);对于不同年龄组的患者,血药浓度随着年龄的增加而增加;对同一年龄组不同性别的患者,女性的血药浓度明显低于男性。结论卡马西平受年龄、性别、药物相互作用等因素的影响,应根据患者基本情况,个体化使用卡马西平,并监测血药浓度,使卡马西平得到更安全、合理、有效的应用。     

银杏叶提取物辅助治疗癫癎33例

目的探讨银杏叶提取物对癫癎的治疗作用。方法将68例癫癎患者随机分为治疗组与对照组,对照组按不同发作类型分别服用苯妥英钠、丙戊酸钠、卡马西平等;治疗组在对照组的基础上加用银杏叶提取物40mg,tid,小儿按体重给药,均用药3个月。结果治疗组显效率及总有效率显著优于对照组(P＜0.01与P＜0.05),治疗前后自身对照(P＜0.05)。结论银杏叶提取物通过多种途径抑制癫癎发作,是一种较好的辅助抗癫癎药。     

12009例癫患者血清丙戊酸钠浓度测定结果分析

目的通过汇总分析丙戊酸血浆浓度监测结果,探索癫患者的用药状况。方法调查某院1999～2008年12 009例癫患者使用丙戊酸后血浆浓度监测数据,并按性别、年龄作统计分析。结果从10 a统计数据看,丙戊酸血浆浓度监测数男性多于女性,差异有统计学意义(P<0.01);丙成酸血药浓度在50～100 mg.L-1为48.6%,血药浓度<50 mg.L-1为46.0%,血药浓度>100 mg.L-1为5.4%;自2006年以来,<3岁癫患者出现了大幅度的增加,而且血药浓度不在有效浓度范围的比有较高。结论加强血药浓度监测,尤其是对<3岁患儿的血药浓度监测、深化合理用药方案研究十分必要。     

硫酸镁辅助治疗顽固性癫癎72例

目的探讨硫酸镁辅助治疗顽固性癫癎的剂量、方法及疗效。方法治疗组72例,用25%硫酸镁10mL静脉滴注,或用16.5%硫酸镁10mL口服。对照组36例给予常规抗癫癎药物,卡马西平或苯妥英钠加苯巴比妥或氯硝西泮加用γ-氨基丁酸等治疗。结果治疗组有效率87.5%,对照组有效率44.4%,两组比较经统计学分析P＜0.01,差异极显著。结论硫酸镁联合一线抗癫癎药治疗顽固性癫癎的方法简单易行,具有良好效果。     

奥卡西平和卡马西平对致(痫)大鼠认知功能的影响

目的 观察卡马西平、奥卡西平对癫(痫)认知功能的影响.方法 采用随机数字表方法将实验大鼠分为对照组、致(痫)组、奥卡西平组及卡马西平组,每组各20只.对照组用0.9％氯化钠注射液造模;致(痫)组用氯化锂-匹罗卡品造模,不服用药物;奥卡西平组用氯化锂-匹罗卡品造模,并用奥卡西平200 mg/d灌胃;卡马西平组用氯化锂-匹罗卡品造模,并用卡马西平200 mg/d灌胃,通过Morris水迷宫实验测试并记录逃避潜伏期和平台象限游泳时间.实时聚合酶链反应(RT-PCR)法检测ERK-2 mRNA、NCAM-1 mRNA表达,免疫组织化学化法检测细胞外调节蛋白激酶2 (ERK-2)蛋白、神经细胞黏附分子1(NCAM-1)蛋白表达(阳性神经元计数).结果 训练初期,卡马西平组、奥卡西平组、致(痫)组、对照组逃逸潜伏期平均时间、平台象限游泳时间分别为(81±9)和(27±9)s,(72 ±9)s和(32±14)s,(67 ±7)s和(37±13),(36±5)s和(51 ±11)s,卡马西平组、奥卡西平组、致(痫)组和对照组比较,差异均有统计学意义(均P＜0.01).卡马西平组、奥卡西平组、致(痫)组、对照组NCAM/β3-actin和ERK-2 /β3-actin分别为0.60±0.12和0.43 ±0.11、0.66 ±0.03和0.51±0.17、0.95 ±0.21和0.59±0.24、0.48±0.04和0.75 ±0.23,卡马西平组、奥卡西平组的大鼠海马组织NCAM-1 mRNA表达水平明显低于致(痫)组(P＜0.01).致(痫)组中ERK-2的mRNA表达水平明显低于对照组(P＜0.01).卡马西平组、奥卡西平组的大鼠海马组织中ERK-2表达水平明显低于致(痫)组(P＜0.01).结论 ERK-2在癫(痫)发作1个月时在海马的表达水平下降,NCAM-1则相反.二者均参与了癫(痫)认知功能障碍的发病,卡马西平能加重癫(痫)认知功能障碍,奥卡西平对癫(痫)认知功能障碍影响轻微.     

高效液相色谱法同时测定苯巴比妥、苯妥英、卡马西平、茶碱的血药浓度

目的:建立以高效液相(HPLC)色谱法同时测定苯巴比妥、苯妥英、卡马西平、茶碱血药浓度的方法.方法:苯巴比妥、苯妥英、卡马西平、茶碱血浆样品,经二氯甲烷提取,测定苯巴比妥、卡马西平、茶碱的血药浓度以苯妥英为内标,测定苯妥英的血药浓度以卡马西平为内标,流动相:甲醇-水(60:40),柱温40℃,检测波长:210 nm,流速:1.0 mL·min-1.结果:苯巴比妥、苯妥英、茶碱、卡马西平分别在2.5～40 mg·L-1,2.5～40mg·L-1,2.5～40 mg·L-1,1.25～40 mg·L-1范围内的线性关系良好,日内和日间RSD＜10%(n=5).结论:该方法具有良好的准确性、精密性和较高的灵敏度,且简便、快速、稳定,适用于苯巴比妥、苯妥英、卡马西平、茶碱治疗药物血药浓度监测.     

乳酸左氧氟沙星对肺心病人体内茶碱药动学的影响

应用紫外分光光度法分别测定8例肺心病患者单独静脉滴注氨茶碱及合用乳酸左氧氟沙星达稳态后茶碱的血药浓度,发现乳酸左氧氟沙星明显延长了茶碱的半衰期(P＜0.01),使茶碱达稳态时血药浓度明显升高(P＜0.01),清除率(CL)下降(P＜0.01).提示临床两药合并应用时,应加强茶碱的血药浓度监测,调整用药剂量.     

NONMEM法估算中国癫痫患者卡马西平的清除率

目的　考察中国癫痫患者卡马西平的群体药动学参数。方法　癫痫病例来自上海、北京两地 4所医院 ,采集服用卡马西平的 5 92例患者的稳态血药浓度 (n =70 3)。NONMEM程序估算分析时 ,采用一级吸收和消除的药动学模型并固定吸收速率、生物利用度和表观分布体积参数。结果　体重 (TBW )、剂量 (Dose)、合用丙戊酸钠 (VPA)且其日剂量大于 2 0mg·kg-1·d-1、苯妥英 (PHT)、苯巴比妥 (PB)和年龄大于 6 5岁的老年人 (ELDER)均为卡马西平清除率(CL)的影响因素。性别、合用氯硝西泮、妥吡酯不改变卡马西平的清除率。最终模型为 :CL(CL/F) (L/h) =1 32·Dose(g·kg-1·d-1) 0 42 1·TBW (kg) 0 .691·1 2 0 VPA·1 4 3PHT·1 14 PB·0 836 ELDER。讨论　根据中国癫痫患者的群体药动学模型 ,结合患者服用的剂量、体重和合并用药可估算其清除率 ,制定给药方案     

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。     

癫痫患者血清与唾液中卡马西平浓度的相关性研究

目的:研究卡马西平在癫痫患者血清与唾液中药物浓度的相关性,探索用唾液监测卡马西平药物浓度的可行性。方法:采用高效液相色谱法测定卡马西平在癫痫患者血清、血清超滤液和唾液中的浓度,按年龄(分为未成年和成年组)和剂量(分为小剂量和大剂量组)分组后,用SPSS12.0软件对数据进行相关性分析。结果:未成年组与成年组、大剂量组与小剂量组的血清与唾液中卡马西平浓度的相关性系数分别为r未成年=0.492与r成年=0.862、r小剂量=0.572与r大剂量=0.846,血清、血清超滤液与唾液中卡马西平浓度的相关性系数分别为r血清/唾液=0.601、r血清超滤液/唾液=0.806。结论:对于成年组和大剂量组,卡马西平在血清和唾液中浓度呈线性相关(r>0.84),且癫痫患者唾液中的药物浓度与血清中的游离药物浓度相关性更好。因此,本试验为临床上采用唾液法进行卡马西平浓度监测提供了一定的试验依据。     

丙戊酸钠与苯妥英钠或卡马西平相互作用的血浓度观察

本文报告丙戊酸钠和苯妥英钠或卡马西平合用治疗各型癫痫９０例，丙戊酸钠使苯妥英钠和卡马西平血浓度下降；苯妥英钠和卡马西平是强有力的肝酶诱导剂，使丙戊酸钠血浓度降低，作者认为，抗癫痫药之间的相互作用错综复杂，临床上最好选择单一用药，昼避免联合用药。     

Factors influencing simultaneous concentrations of total and free carbamazepine and carbamazepine-10, 11-epoxide in serum of children with epilepsy

Various factors that may influence the simultaneous concentration of total and free carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) in serum of 68 children (mean age 11.8 +/- 4.5 years) with epilepsy were assessed. Separation of free and bound drug fractions was achieved by ultrafiltration, and CBZ and CBZ-E concentrations were determined using a sensitive high pressure liquid chromatographic technique. Thirty children were on CBZ monotherapy. Both total CBZ and CBZ-E serum concentrations correlated significantly with their respective free serum concentrations. CBZ was 81 +/- 3% and CBZ-E 63 +/- 9% bound. There was no correlation between the CBZ dose and either CBZ total or free serum concentrations. A statistically significant correlation was, however, observed between CBZ dose and simultaneous CBZ-E total and free concentrations. CBZ total and free concentrations correlated significantly with those of total CBZ-E. A significant negative correlation was observed between age and total (r = -0.49, p less than 0.01) and free (r = -0.43, p less than 0.025) CBZ-E/CBZ ratios. Concomitant drug therapy (phenytoin, phenobarbitone, and sodium valproate) significantly elevated CBZ-E/CBZ ratios.     

游离药物浓度监测指导癫患者联合用药

摘要目的指导癫患者合理用药。方法观察西安交通大学医学院第二附属医院2007～2010年服用丙戊酸（VPA）和卡马西平（CBZ）癫患者3 906例,其中抽取100例监测游离药物浓度。结果VPA和CBZ联合用药相比单一用药时,VPA浓度在有效浓度范围内的比例由72.5%降低至54.8%,CBZ浓度在有效浓度范围内的比例由58.0%增加至84.3%。单用或联合用药时,在高浓度VPA和CBZ的蛋白结合率明显下降,游离浓度增加。结论VPA和CBZ在联合用药时要根据血药浓度监测结果调整给药剂量,在高浓度时应监测游离药物浓度。     

Serum concentrations of carbamazepine and its epoxide and diol metabolites in epileptic patients: the influence of dose and comedication

The influence of carbamazepine (CBZ) dose, CBZ preparation used, comedication (phenobarbital, phenytoin, primidone, valproate), and factors such as age, weight, and sex on the concentration of CBZ and its metabolites carbamazepine-10,11-epoxide (CBZ-epoxide) and 10,11-dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in serum was investigated. A non-linear regression analysis using the data of 609 patients shows that other anti-epileptic drugs can influence the metabolism of CBZ in various ways. The mean serum concentration of CBZ is lower when the drug is given in combination with phenytoin (59.4%), primidone (58.2%), phenobarbital (65.7%), and valproate (83.0%) than when CBZ is given alone (100%), whereas the mean concentration of CBZ-epoxide is increased by valproate (144.8%), by primidone (118.5%), and by a combination of the latter (167.4%). The CBZ-diol concentrations are also increased during concomitant treatment with the other antiepileptic drugs. Our results indicate a nonlinear relationship between the CBZ dose and the CBZ concentration, but a linear relationship between the CBZ dose and the CBZ-diol concentration.     

Alpha1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10,11 epoxide in children with epilepsy

Summary The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of ₁-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years.A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.     

Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues.

1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine.     

比较HPLC和FPIA法测定人血清中卡马西平的血药浓度

目的比较治疗药物监测中高效液相色谱法(HPLC)和荧光偏振免疫法(FPIA)测定血清中卡马西平(CBZ)的浓度。方法收集上海华山医院和北京天坛医院服用CBZ的癫痫患者608例的稳态谷浓度血样,分别用HPLC法和FPIA法进行测定,用回归法和图解法考察2种测定方法的相关程度以及环氧化卡马西平(CBZE)的交叉反应率。结果CBZE能干扰CBZ的测定,CBZ测定值FPIA较HPLC法高4.58% (95%置信区间:-5.7%~17.6%)。CBZE的交叉反应率随CBZE浓度增加而减小。结论 在CBZ治疗药物监测中,对不同测定方法测定差异,应予以关注并作相应调整。     

Protein binding of antiepileptic drugs during pregnancy, labor, and puerperium

Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum.