联合用药对卡马西平血浓度及临床疗效的影响

采用高性能液相色层分析法对１１８例服用卡马西平的癫痫患儿测定了血卡马西平（ＣＢＺ）及其中间代谢产物１０、１１－环氧卡马西平（Ｅ－ＣＢＺ）药浓度。７８例单用ＣＢＺ，４０例合用其他抗痫药，其中１５例合用苯巴比妥（ＰＢ）、７例合用苯妥英钠（ＰＨＴ）、１０例合用丙戊酸钠（ＶＰＡ－Ｎａ）、８例合用硝基安定（ＮＴＺ）。各组ＣＢＺ平均给药剂量相似。结果表明，合用ＰＢ或ＰＨＴ组血ＣＢＺ药浓度与临床疗效明显低于单药组（Ｐ＜０．０１）。合用ＶＰＡ－Ｎａ组血ＣＢＺ浓度与单药组无显著差异，Ｅ－ＣＢＺ血浓度明显高于单药组（Ｐ＜０．０１），而临床疗效低于单药组（Ｐ＜０．０５）。合用ＮＴＺ组血ＣＢＺ及Ｅ－ＣＢＺ浓度与临床疗效与单药组比较，差异均无显著意义（Ｐ＞０．０５）。提示ＣＢＺ抗痫治疗不宜与ＰＢ或ＰＨＴ合用，Ｅ－ＣＢＺ浓度与临床疗效无相关性。     

抗癫癎药物对维生素D代谢的影响

目的：探讨3种小儿常用抗癫痫药（苯巴比妥、卡马西平及丙戊酸钠）对癫痫患儿维生素D代谢的影响。方法：用放射免疫法检测癫痫服药患儿及对照组儿童血清25－（OH）D3水平。结果：各抗癫痫药组与对照组相比，25－（OH）D3均显著降低（P＜0．01）。结论：上述小儿常用3种抗癫痫药物，均可影响患儿体内维生素D的正常代谢。     

几种抗癫痫药物抗癫痫作用耐受性的观察

几种抗癫痫药物抗癫痫作用耐受性的观察北京医科大学第一医院儿科研究室（北京，１０００３４）王晓军王丽苯巴比妥（ＰＢ）、丙戊酸（ＶＰＡ）、卡马西平（ＣＢＺ）及苯二氮艹卓类（ＢＺＤｓ）药物是儿科临床常用抗癫痫药物，但是经过一段时间的给药，可见到上述药物抗癫...     

抗癫(癎)药高敏综合征11例报告

现将本院近4年诊断的11例抗癫癎药高敏综合征(AHS)报道如下。一般资料:11例患儿均系在本院癫癎门诊就诊的癫癎患儿,其中男性6例,女性5例。年龄在1岁11个月至9岁8个月之间,中位年龄6岁6个月。2例出生时窒息。3例合并支气管哮喘,3例对青霉素或解热止痛药过敏。11例癫癎患儿中除3例全身强直阵挛发作外余8例均为部分性发作。2例多药治疗,分别是苯巴比妥钠加卡马西平和丙戊酸钠加卡马西平联合应用,9例单药治疗中3例口服苯巴比妥钠,6例口服卡马西平。临床表现:开始服用抗癫癎药到出现AHS的时间仅1例5个月,其余均在1个月以内,最短仅9d,中位天数2…     

三种抗癫(癎)药物单药首治伴中央-颞区棘波的儿童良性癫(癎)的疗效对比

目的 丙戊酸钠、卡马西平、托吡酯被公认为是目前广谱的抗癫(癎)药物,临床上均可用于治疗伴中央-颞区棘波的儿童良性癫(癎)(BECT).本研究旨在比较这些药物对儿童BECT的治疗效果,筛选临床单药治疗的首选药物.方法 通过84例药物治疗BECT病例(丙戊酸钠31例,卡马西平31例,托吡酯22例)的回顾性分析,从首药治疗失败时间、首治发作控制率、药物不良反应三个方面,对托吡酯、卡马西平、丙戊酸钠的治疗效果进行比较.结果 托吡酯、卡马西平、丙戊酸钠的首药治疗失败时间分别为3.00个月[0.75～12.00]、8.00个月[2.50～32.00]、5.00个月[1.25～11.75],三者差异无显著性(P=0.463).癫(癎)发作控制率托吡酯、卡马西平、丙戊酸钠分别为77.3%、83.9%、74.2%,差异无显著性(X2=1.475,P=0.478).托吡酯有较高的药物不良反应发生率,与丙戊酸钠(X2=8.717,P=0.003)和卡马西平(X2=7.105,P=0.008)相比差异有显著性,丙戊酸钠与卡马西平相比差异无显著性(X2=0.111,P=0.74).结论 托吡酯、卡马西平、丙戊酸钠均可作为儿童BECT单药治疗的首选药物.     

肥胖癫痫患儿卡马西平药代动力学研究

目的　研究癫痫患儿口服卡马西平的药代动力学,并比较肥胖癫痫患儿与正常体重癫痫患儿的代谢情况。方法　对１５ 例癫痫患儿进行口服卡马西平药代动力学参数测定,按体重分组比较肥胖患儿与正常体重患儿的药物消除特点,其血药浓度采用高效液相色谱法测定。结果　１５ 例患儿口服卡马西平药动学参数为表观分布容积（１－４３ ±０－４５）Ｌ／ｋｇ,消除半衰期（２１－２５ ±１０－０９）ｈ,清除率（５１－７２ ±２０－３０）ｍｌ／（ｋｇ·ｈ）。肥胖患儿比正常体重患儿的药物消除半衰期延长,清除率降低。结论　肥胖患儿卡马西平代谢速率慢于正常体重患儿。     

癫癎儿童拉莫三嗪的群体药代动力学研究

目的：用NONMEM软件建立中国癫癎儿童拉莫三嗪（LTG）的群体药代动力学（PPK）模型。方法：回顾性收集服用LTG的癫癎165名患儿的303份血样浓度数据及临床资料,血药浓度为临床常规监测的稳态浓度,采用反相高效液相色谱法测定。应用PPK专业软件NONMEM,按照一室一级吸收和消除模型,建立我国癫癎儿童LTG的PPK模型。用平均预测误差（ME）、标准平均预测误差（SME）、平均方差（MSE）、平均根方差（RMSE）及加权残差（WRES）作为模型预测准确程度和精密程度的评价指标,对基础模型和最终模型的预测效能进行比较。结果：LTG的基础模型为：CL/F=0.664×EXP［ETA(1)］,V/F=45×EXP［ETA(2)］,KA=4.0×EXP［ETA(3)］;最终回归模型为：CL/F=0.717×(1-0.601×VPA)×(1+1.18×EI)×［1.62∧(AGE/7.02)］×EXP［ETA(1)］,V/F=40.2×EXP［ETA(2)］,KA=3.27×EXP［ETA(3)］。CL/F、V/F、KA的群体典型值分别为1.16 L/h(0.042 L/h?kg)、40.2 L(1.46 L/kg)和3.27/h。经过内部验证和外部验证,所建立的最终模型有良好的稳定性和预测效能。结论：应用NONMEM软件成功地建立了我国癫癎儿童LTG的PPK模型,可准确的预测LTG血药浓度,促进了个体化给药方案的实施。     

抗癫癎药物的血药浓度监测与疗效的关系

目的通过血药浓度监测分析抗癫癎药物(AEDs)临床疗效与血药浓度之间的关系,为临床个体化合理用药提供依据。方法采用荧光免疫偏振分析法对226例癫癎患儿进行了576例次的AEDs血药浓度监测,并对其相应的疗效、药物的肝损伤及其关系进行分析。结果在有效的血药浓度范围内,各类药物对癫癎的控制率为:丙戊酸钠78.1%,鲁米那52.4%,卡马西平42.3%,丙戊酸钠 氯硝西泮55.6%,苯妥英那25%。肝损伤发生率4.9%(11/226例),其中丙戊酸钠引起的占63.6%,但仅占丙戊酸钠例次的1.5%。结论血药浓度监测是指导儿童癫癎治疗的重要指标,在本组AEDs中丙戊酸钠疗效最佳。     

丙戊酸钠治疗儿童失神癫的疗效

目的观察丙戊酸钠单剂治疗儿童失神癫的疗效。方法选择1990-04—2004-05在首都儿科研究所儿童医院诊断失神癫并首选口服丙戊酸患儿123例,发作未能完全控制者加用氯硝西泮,观察其疗效并进行追踪。结果123例患儿中,丙戊酸单药治疗后发作完全控制者105例,发作完全控制率84.4%,其余18例单用丙戊酸发作未能完全控制者,加用氯硝西泮后,发作均得到完全控制,全部患儿发作完全控制率为100%。追踪34例停药后的患儿9个月至10年,其中2例复发,占5.9%。结论丙戊酸单药治疗失神癫能使84.4%的患儿发作完全控制,发作不能完全控制者应加用氯硝西泮,二者联合用药可使患儿的临床发作得到完全控制,且起效快。     

左乙拉西坦、丙戊酸钠、苯巴比妥预防大鼠反复热性惊厥疗效观察

目的：比较左乙拉西坦、丙戊酸钠、苯巴比妥对大鼠反复热性惊厥的预防作用的差异,指导临床选药。方法：60只Wistar大鼠,随机分为4组,分别每日灌服左乙拉西坦（200 mg/kg）、丙戊酸钠（250 mg/kg）、苯巴比妥（30 mg/kg）及生理盐水（8 mL/kg）。连续灌服5 d后,用热水浴（45℃）诱导热性惊厥,观察其热性惊厥潜伏期、惊厥持续时间、惊厥严重程度改变情况。结果：大鼠用药后,3个药物干预组惊厥潜伏期延长、惊厥持续时间缩短,惊厥严重程度也明显减轻,与对照组比较差异有统计学意义（P＜0.05或0.01）,其中苯巴比妥组惊厥持续时间最短,惊厥严重程度最轻;左乙拉西坦组与丙戊酸钠组差异无统计学意义。结论：左乙拉西坦与丙戊酸钠、苯巴比妥比较均能有效预防大鼠反复热性惊厥,其中苯巴比妥疗效较好,左乙拉西坦与丙戊酸钠疗效无差异。［中国当代儿科杂志,2010,12（7）：573-575］     

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目的建立中国癫痫儿童左乙拉西坦(LEV)群体药代动力学(PPK)模型,指导临床合理用药。方法分析2009年6月至2010年12月北京大学第一医院小儿神经门诊及病房收集的220例服用LEV癫痫患儿的250个LEV血药浓度数据,使用非线性混合效应模型(NONMEM)软件,按照一室一级吸收和消除模型,建立我国癫痫患儿LEV的PPK模型。使用正态化预测分布误差(NPDE)方法验证模型。结果 LEVPPK基础模型:清除率(CL/F)=1.56×EXP[ETA(1)]L/h,表观分布容积(V/F)被固定为20L,吸收速率常数(KA)=EXP[ETA(3)]/h;最终模型:CL/F=[1.35×(体重/25.26)0.578]L/h,V/F=20L,KA=2.11×EXP[ETA(3)]/h;CL/F、V/F和KA群体值分别为1.35L/h、20L和2.11/h。经过NPDE方法验证,所建立的最终模型有良好稳定性和预测效能。结论本文建立了中国癫痫患儿LEVPPK模型,模型通过验证及预测效能,可用于指导临床用药。体重是对清除率影响最明显的协变量。     

Serum lipid profile in children receiving anti-epileptic drug monotherapy: is it atherogenic?

The effect of anti-epileptic drugs (AEDs) on serum lipid profile is controversial in children as well as in adults. We longitudinally studied serum lipid profile in 34 newly diagnosed epileptic children receiving AED monotherapy with valproic acid (VPA), carbamazepine (CBZ) or phenobarbital (PB). Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein Al (Apo A1) and apolipoprotein B (Apo B) were measured at baseline and after 2 years of AED monotherapy. Atherosclerotic indices of TC/ HDL-C and Apo A1/Apo B ratios were calculated. Although there were some alterations in serum lipid profile with AED without statistical significance, the atherosclerotic indices of TC/HDL-C and Apo A1/Apo B ratios did not change significantly after 2 years of monotherapy. Only serum TGs levels significantly decreased with VPA monotherapy. These data suggest that 2 years AED monotherapy with VPA, CBZ or PB did not cause a significant level of concern for an atherogenic effect in children with epilepsy.     

Reduced carnitine and antiepileptic drugs: cause relationship or co-existence?

Serum carnitine was measured longitudinally before and after therapy in 15 patients receiving valproic acid, 14 patients receiving carbamazepine and 8 patients receiving phenobarbital. The patients who received valproic acid showed a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2)/umol/l without valproic acid, 29.1 (1.6)/xmol/l with valproic acid (p < 0.001)). Such an effect was not found in patients receiving carbamazepine or phenobarbital.     

Phenobarbital compared with carbamazepine in prevention of recurrent febrile convulsions. A double-blind study

In a double-blind trial, children who had recurrent and/or complex febrile convulsions were treated with either phenobarbital sodium or carbamazepine. Forty children were suitable for analysis; 19 were receiving carbamazepine, and 21 were receiving phenobarbital. Of the carbamazepine-treated patients, nine (47%) had recurrent convulsions despite therapeutic levels of the drug, while only two (10%) of the phenobarbital-treated patients suffered further seizures. These results confirm previous findings suggesting that carbamazepine is not as effective in the prophylactic treatment of febrile convulsions as phenobarbital.     

Population pharmacokinetics of high dose ibuprofen in cystic fibrosis

Methods: Blood samples were collected during routine clinical care; serum ibuprofen concentrations were determined by HPLC. Fitting of the concentration/time data to a one compartment kinetic population model was performed by a non-linear mixed effect regression method. Results: Body weight, dose, and ibuprofen dosage form (lysinate salt or the free acid form), for elimination clearance (CL/F); and body weight, dose, and fasting status for the apparent distribution volume (Vd/F) proved to be the covariates with influence in the model. The four factors identified helped to explain part of the interindividual variability observed, but the remaining unexplained variability made therapeutic drug monitoring absolutely essential.     

Oxidative stress in children receiving valproic acid

OBJECTIVE: To determine whether valproic acid (VPA) influences urinary levels of 15-F2t -isoprostane (15-F2t -IsoP), a marker of oxidative stress, in children. STUDY DESIGN: Morning urine samples were collected from children with epilepsy receiving VPA (n = 25), carbamazepine (n = 16), or clobazam (n = 12) for > or = 4 weeks and from age-matched control subjects (n = 39). Urinary 15-F2t -IsoP levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean (+/- standard deviation) urine 15-F2t -IsoP levels (nmol/mmol Cr) were: valproic acid (0.36 +/- 0.15); carbamazepine (0.24 +/- 0.10); clobazam (0.23 +/- 0.10); control group (0.20 +/- 0.09). Patients treated with VPA had significantly elevated 15-F2t -IsoP levels when compared with the control, carbamazepine, and clobazam groups (P < .05). Multiple linear regression analysis demonstrated that younger patient age and exposure to second-hand smoke were significant predictors of elevated urine 15-F2t -IsoP levels within the control group (r2 = 0.261, P = .05 and P = .01, respectively). Subjects not exposed to second-hand smoke receiving valproic acid therapy had a significantly elevated mean urine 15-F2t -IsoP level compared to subjects not exposed to second-hand smoke in the carbamazepine, clobazam and control groups (P < .05). CONCLUSIONS: These data demonstrate that treatment of children with VPA is associated with higher urinary levels of 15-F2t -IsoP, a marker of oxidative stress.     

Population pharmacokinetics of high dose ibuprofen in cystic fibrosis.

AIMS: To evaluate ibuprofen population pharmacokinetics in a large series of data collected in children with cystic fibrosis (CF) treated with high doses of ibuprofen (59 patients; 2-18 years), and to identify the main causes responsible for the considerable interindividual variability in ibuprofen serum levels. METHODS: Blood samples were collected during routine clinical care; serum ibuprofen concentrations were determined by HPLC. Fitting of the concentration/time data to a one compartment kinetic population model was performed by a non-linear mixed effect regression method. RESULTS: Body weight, dose, and ibuprofen dosage form (lysinate salt or the free acid form), for elimination clearance (CL/F); and body weight, dose, and fasting status for the apparent distribution volume (Vd/F) proved to be the covariates with influence in the model. The four factors identified helped to explain part of the interindividual variability observed, but the remaining unexplained variability made therapeutic drug monitoring absolutely essential.     

Parental view of epilepsy in Angelman syndrome: a questionnaire study.

PURPOSE: To explore parents' opinions and concerns about seizures, anticonvulsants, and the effect of treatment in children with Angelman syndrome. DESIGN: A postal questionnaire was sent to members of one of the UK lay groups for Angelman syndrome (ASSERT) who had a child affected by Angelman syndrome. The questionnaire requested general medical information and information about the epilepsy, its treatment, and treatment responses. RESULTS: One hundred and fifty questionnaires were sent out with an ASSERT routine mailing and 78 completed questionnaires were returned. Forty three patients were boys and 35 were girls; ages ranged from 1.7 to 25 years (mean 7.5 years). The overall general clinical and cytogenetic data were mostly consistent with previous reports. Epilepsy was reported in 68 children, most of whom had a detectable cytogenetic deletion. The most common seizure types reported by the families were absence seizures, tonic clonic seizures, drop attacks, and myoclonic seizures; in four patients only febrile seizures occurred. The age at onset of the seizures was < 2 years in more than half of the patients. Anti-epileptic drug treatment with valproate (VPA), clonazepam (CZP), and lamotrigine (LTG) as monotherapy or a combination of VPA and CZP or VPA and LTG was more often viewed favourably and considered effective with fewer side effects on the child's behaviour and alertness, versus more frequent adverse effects and increased frequency and severity of seizures with carbamazepine (CBZ) and vigabatrin (VGB) in monotherapy or in combination with other anti-epileptic drugs. Seizures did tend to improve with age but were still present and disabling at older ages. CONCLUSIONS: This is the first study to record parents' opinions about seizures, anti-epileptic drugs, and treatment responses in children with Angelman syndrome, and it is one of the largest series on epilepsy and Angelman syndrome to be reported to date.     

抗癫(癎)药对婴儿痉挛症患儿外周血P-糖蛋白170表达的影响

目的 探讨抗癫(癎)药物(AEDs)对婴儿痉挛症(IS)患儿外周血淋巴细胞中多药耐药基因表达产物P-糖蛋白170(P-gp170)表达水平的影响.方法 应用流式细胞术检测IS患儿P-gp170的表达,根据其治疗方案不同,分为A组(托吡酯,n=6)、B组(丙戊酸钠+托吡酯,n=9)、C组(丙戊酸钠+氯硝西泮,n=6)、D组(托吡酯+氯硝西泮,n=7)、E组(健康对照组,n=8).分别于治疗前、治疗后3个月和6个月检测各组患儿外周血P-gp170表达水平.结果 A、B、C、D组在3个时间点P-gp170表达均较E组显著增高(Pa＜0.001).A、B组3个时间点P-gp170表达水平比较差异均无统计学意义,C、D组6个月时P-gp170表达较治疗前及治疗后3个月显著增高(Pa＜0.05).结论 IS患儿P-gp170外周血表达增高.丙戊酸钠和托吡酯对其表达无明显影响,而氯硝西泮长期应用可能增加P-gp170的表达.