189例癫痫患儿卡马西平血药浓度监测结果分析

目的:评价卡马西平的临床合理应用情况。方法:回顾性分析我院189例癫痫患儿应用卡马西平治疗后的血药浓度监测结果。结果:卡马西平血药浓度<4 mg·L~(-1)者32例,其中20例有效(占62.5%);>12 mg·L~(-1)者2例,2例均有效(达100%);4～12 mg·L~(-1)者155例,其中114例有效(占73.5%)。卡马西平单用治疗组与联合治疗组进行有效率比较,P值均>0.05,尚不能认为卡马西平单用组与联合治疗组的总体有效率有差别。结论:卡马西平血药浓度个体差异很大,应通过对其进行监测,并结合临床疗效制定个体化给药方案。     

RP-HPLC法测定人血浆中卡马西平浓度

目的 建立反相高效液相色谱法测定人血浆中卡马西平浓度的方法.方法 以Agilent TC-C18反相柱(150mm×4.6mm,5μm)为色谱柱,流动相为0.03mol·L-1醋酸铵-乙腈-甲醇(20∶15∶65 V/V/V);流速:0.8mL·min-1;检测柱温:35℃;检测波长:285nm.灵敏度为0.01AUFS.以乙酸乙酯和二氯甲烷 (80∶20 V/V)为提取剂.结果 卡马西平的低、中、高(2.0,8.0,48.0μg·mL-1)3种浓度平均相对回收率分别为101.1%,100.6%,99.89%,提取回收率分别为81.91%,85.02%,88.53%;日内、日间相对标准偏差(RSD)均低于10%(n=5);分析方法的检测限0.5μg·mL-1;线性范围为1.0~64.0μg·mL-1.线性方程:Y=12.512X+1.46,相关系数r=0.9991(n=8).结论 该方法简单、快速、灵敏、准确,可用于卡马西平临床血药浓度监测和药动学研究.     

HPLC法同时测定人血清中卡马西平、环氧化卡马西平和苯妥英

目的:建立同时测定人血清中苯妥英、卡马西平及其代谢物10,11-环氧化卡马西平浓度的HPLC法。方法:用含内标氯唑沙宗的乙腈沉淀样品中蛋白,取上清液进样。分析柱为YWG-C_(18)(4.6mm×200mm,10μm),流动相为乙腈-甲醇-水(13:25:62),检测波长为214 nm。结果:卡马西平、10,11-环氧化卡马西平和苯妥英的标准曲线范围分别为0.4～16,0.2～8,1～40μg·mL~(-1),最低检测浓度分别为0.2,0.1,0.5μg·mL~(-1)。三者的方法回收率近100％,日内和日间精密度均小于6％,内源性物质和常用药物均不干扰测定。结论:该方法操作简便,灵敏、准确,适用于治疗药物监测。     

SPE-GC/MS法检测血液中卡马西平

目的:建立固相萃取提取血液中卡马西平的最佳pH及GC/MS检测血液中卡马西平浓度的方法。方法:通过比较不同pH对回收率的影响,优化用于血中卡马西平固相萃取的条件,利用卡马西平质谱图的分子离子峰面积与卡马西平浓度的定量关系,建立血液中卡马西平的GC/MS定量分析新方法。结果:卡马西平在0.1μg.ml-1-10μg.ml-1范围内线性良好(r=0.9996);在固相萃取中,pH 6.0、7.0、8.0、9.0、10.0、11.0的回收率分别为:51.12%5、7.46%、78.23%8、6.38%、81.42%、73.75%。结论:该固相萃取法提取血液中卡马西平在pH 9.0时回收率最高,此检测方法准确、快速,可以用于血液中卡马西平浓度的检测。     

唾液和血浆中10-羟基卡马西平的药动学及其浓度的相关性研究

目的:考察唾液与血浆中10-羟基卡马西平的药动学及其浓度的相关性。方法:20名志愿者禁食1晚后,服用奥卡西平600mg,在96h内同步收集血液和静息唾液样本,用已建立的高效液相色谱方法对10-羟基卡马西平进行分析。结果:唾液和血浆中10-羟基卡马西平的AUC_(0～∞)分别为(162±s 86)和(186±27)mg·h·L~(-1)。c_(m(?))分别为(8．1±1．4)和(7．2±1．3)mg·L~(-1),t_(max)分别为(4．7±2．7)和(5．4±1．5)h,t_(1/2)为(11．1±2．5)和(10．2±1．7)h,MRT_(0～(相似文献   

高效液相色谱法测定人血清中卡马西平及环氧化卡马西平浓度

目的建立测定人血清中卡马西平及其代谢物10,11-环氧化卡马西平浓度的方法.方法采用高效液相色谱法,血样用乙醚提取,以艾司唑仑为内标,色谱柱为Kromasil C18柱(150 mm ×4.6 mm,5μm),流动相为乙腈-水(1:2),检测波长215 nm,流速1.2ml·min-1.结果血清中卡马西平、环氧化卡马西平线性范围分别为1.0～20.0 mg·L-1(r=0.999 9)、0.1～5.0 mg·L-1(r=0.999 4),平均回收率接近100%,日内、日间RSD均小于5%.结论本法快速、简便、准确,适用于临床常规监测需要.     

评价卡马西平引发低钠血症的风险

报告1例卡马西平引起低钠血症而造成癫痫发作的事例。1例44岁妇女两次服用卡马西平的晚间剂量（通常为600mg）后，引发急性低钠血症和随后的强直阵挛性癫痫发作。入院时血钠水平为122mEq·L^-1。开始滴注0．9％氯化钠，24h内血钠水平恢复到以前的136m·Eq·L^-1。病人入院时的卡马西平浓度是8．6mg·ml^-1，入院后浓度是11．3mg·ml^-1，停止服用卡马西平后卡马西平的浓度为5．6mg·ml^-1。6个月前该妇女服用大剂量卡马西平时，也发生过同样的事件。作者确认在其他造成低钠血症的风险因素存在时，大剂量服用卡马西平是会引发低钠血症和癫痫发作的。[第一段]     

单用不同剂量托吡酯与卡马西平治疗老年癫痫发作的疗效比较

目的:观察单用不同剂量托吡酯及卡马西平治疗老年癫痫病人的临床疗效和不良反应,探讨单用托吡酯更安全、更有效的给药方法。方法:老年癫痫病人120例,分为卡马西平组,31例,服用卡马西平(200～ 600 mg·d~(-1));单用托吡酯组,89例病人按服药剂量不同又分为,低剂量组47例(托_1组,100～200 mg·d~(-1)),高剂量组42例(托_2组,300～400 mg·d~(-1)):结果:托_1,组总有效率81％,托_2组总有效率74％;卡马西平组总有效率77％,3组比较无显著差异(P>0．05)。托_2组不良反应发生率(57％)高于托_1组(34％)(P<0．05)。托吡酯组主要不良反应为感觉异常、胃纳差、头痛、嗜睡头晕和体重减轻。结论:单用较小剂量托吡酯(100～ 200 mg·d~(-1))治疗老年癫痫发怍,疗效好,不良反应少而且轻。     

铈(Ⅳ)-亚硫酸钠体系化学发光分析法测定卡马西平

目的:建立一种测定片剂卡马西平含量的化学发光分析新方法。方法:在酸性条件下,卡马西平对铈(Ⅳ)和亚硫酸钠弱的化学发光有明显的增敏作用,并结合流动注射技术,建立了流动注射化学发光分析法测定卡马西平的新方法。结果:在优化的实验条件下,增敏的化学发光强度ΔI与卡马西平浓度在1.00×10-8～1.00×10-6g·mL-1的范围内呈良好的线性关系,检出限为6.0×10-9g·mL-1,RSD片剂含量测定;增敏为3.4%(3.0×10-7g·mL-1,n=11),并成功地应用于片剂中卡马西平含量的测定。结论:本方法操作简单且快速,适合于卡马西平的分析。     

LC-MS/MS法测定癫痫患者血清中卡马西平的浓度

目的:建立以高效液相色谱-电喷雾串联质谱(LC-MS/MS)法测定癫痫患者血清中卡马西平浓度的方法。方法:色谱柱为Zorbax Extend-C18,流动相为甲醇-0.01mmol.L-1乙酸铵溶液(80:20),流速为0.3mL.min-1,进样量为10μL;离子源为电喷雾离子化源,正离子方式检测,扫描方式为正离子监测,卡马西平的碰撞诱导解离电压为30V,用于定量分析的离子反应为m/z237.2→m/z194.2。结果:卡马西平血药浓度在2.0～40.0ng.mL-1范围内线性关系良好(r=0.9974);平均提取回收率为101.1%,日内、日间RSD分别为3.39%、4.11%。10名患者血清中卡马西平的平均浓度为5.69ng.mL-1(RSD=4.75%),比荧光偏振免疫法测定结果的RSD小。结论:本方法专属性强,灵敏度和准确度、重现性好,易于操作,可用于癫痫患者血清中卡马西平浓度的测定。     

Quantification of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples by stir bar-sorptive extraction and liquid chromatography

A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C(18) column with UV detection (210nm). The mobile phase consisted of water:acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0mugmL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0mugmL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125mugmL(-1) for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method.     

Performance of techniques for measurement of therapeutic drugs in serum. A comparison based on external quality assessment data.

Ten assay techniques were compared using measurements of a range of 15 drugs spiked in freeze-dried samples of serum reported to the Heathcontrol External Quality Assessment Scheme between November 1988 and January 1991. Three measures of performance were studied: frequency of outliers greater than 3 standard deviations from the sample mean, the coefficient of variation (CV) of sample measurements, and the difference of the sample mean from the spike value. The most consistently precise technique was polarisation fluoroimmunoassay (PFIA). It was in the group of techniques producing significantly fewer outliers and lower CVs than other techniques for all its target analytes. However, a specific interaction with the animal serum used as sample matrix resulted in significant negative bias in PFIA measurements of carbamazepine. Other immunoassay techniques and high-performance liquid chromatography also performed well for a range of analytes, in most cases giving less than 6% of outliers with CVs of less than 13% and less than 5% bias. The least satisfactory techniques were nephelometry and gas-liquid chromatography with derivatisation, which for several analytes gave significantly more outliers and higher CV values than other techniques. In samples containing carbamazepine-10, 11-epoxide, immunoassay measurements of carbamazepine showed cross-reactivity with the epoxide metabolite of between 7 and 15%.     

Erythromycin effects on multiple-dose carbamazepine kinetics

To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.     

The mechanism of the carbamazepine-valproate interaction in humans

Aims The study investigated the mechanism of the interaction between valproate and carbamazepine which causes raised plasma carbamazepine-10,11-epoxide concentrations with unchanged plasma carbamazepine concentrations. This interaction has usually been attributed to valproate inhibiting epoxide hydrolase, the enzyme that catalyses the biotransformation of carbamazepine-10,11-epoxide to carbamazepine-10,11-trans-diol.
Methods Clearances of plasma carbamazepine, carbamazepine-epoxide and carbamazepine-diol to relevant carbamazepine metabolites present in urine were measured under steady-state conditions in 17 adults receiving carbamazepine as anticonvulsant monotherapy, and in 10 adults taking the drug together with valproate.
Results Plasma carbamazepine-epoxide concentrations were higher, relative to carbamazepine dose, in the co-medicated patients. Plasma apparent clearances of carbamazepine, relative to drug dose, were similar whether or not valproate was taken. Formation clearances of carbamazepine-10,11-trans-diol conjugate, and probably of carbamazepine-10,11-trans-diol, were lower in subjects co-medicated with valproate, and a higher proportion of the carbamazepine dose was excreted in urine as carbamazepine-10,11-epoxide.
Conclusions Valproate appears to inhibit the glucuronidation of carbamazepine-10,11-trans-diol, and probably also inhibits the conversion of carbamazepine-10,11-epoxide to this trans-diol derivative, rather than simply inhibiting the latter reaction only.     

Does carbamazepine-epoxide conjugate with glutathione? On an existing but almost forgotten possibility

The anticonvulsant carbamazepine is widely used to treat affective disorders and behavioural disorders in non-epileptic children. We report an elevated plasma level of carbamazepine-10,11-epoxide in a cystinuric child after daily medication with 300 mg carbamazepine while the serum level of carbamazepine was in the therapeutic range. The concentrations of carbamazepine and its epoxide derivative were determined by HPLC. The formation of a glutathione conjugate of carbamazepine-10,11-epoxide is raised as a hypothesis.     

高效液相色谱法同时测定人血浆中卡马西平、奥卡西平及其活性代谢产物的浓度和临床应用

目的：建立同时测定人血浆中卡马西平（CBZ）、10,11-环氧卡马西平（CBZE）、奥卡西平（OXC）和单羟基卡马西平（MHD）浓度的高效液相色谱法,并将其应用于临床中卡马西平、奥卡西平及其活性代谢产物血药浓度的测定。方法：以苯巴比妥为内标,血浆经乙醚-二氯甲烷（2∶1）提取。色谱柱为WondaSil C₁₈柱（150 mm×4.6 mm,5 μm）,流动相为甲醇∶水=50∶50,柱温30℃,流速1.0 mL·min^-1,检测波长215 nm,进样量20 μL。结果：卡马西平、10,11－环氧卡马西平、奥卡西平和单羟基卡马西平标准曲线范围分别为0.1~20,0.05~10,0.05~20,0.2~50 mg·L^-1,最低检测限分别为0.1,0.05,0.05,0.2 mg·L^-1,日内、日间精密度均小于10%。结论：该方法灵敏准确,简便快速,适用于卡马西平、奥卡西平及其代谢产物血药浓度检测。     

Carbamazepine and its 10,11-epoxide in children and adults with epilepsy

Summary The plasma concentrations of carbamazepine and its 10,11-epoxide were measured in 37 children and 13 adults with epilepsy during maintenance therapy. The children formed relatively more of the epoxy metabolite than adults. The daily dose, expressed as mg/kg or mg/m², showed a statistically significant correlation with blood level in children, but not in adults. The cerebrospinal fluid concentrations of carbamazepine and carbamazepine-10,11-epoxide in nine children were 33 and 41 per cent, respectively, of the concomitant plasma level.     

甘草对大鼠体内卡马西平药代动力学的影响

目的：研究甘草对卡马西平及其代谢产物10,11-环氧卡马西平在大鼠体内的药代动力学影响。方法：12只实验大鼠随机分为生理盐水对照组和甘草实验组,甘草提取物（0.5 g/kg,1次/d）连续给药7 d后,卡马西平灌胃给药后按时间点连续采样,采用HPLC法测定卡马西平及其代谢产物。计算并比较主要药动学参数。结果：对照组和实验组的卡马西平主要药动学参数Cmax、tmax、t1/2、AUC0→24 h、AUC0→∞、MRT差异均无统计学意义（P〉0.05）,而10,11-环氧卡马西平的Cmaxt、max和AUC0→24 h同样无统计学意义（P〉0.05）。结论：甘草连续给药7 d后不影响卡马西平在大鼠体内的药代动力学。     

Effects of carbamazepine on hepatic glutathione level in rats and determination of carbamazepine and its epoxide metabolite in plasma by HPLC

We investigated whether carbamazepine, which is known to be metabolized to an electrophilic epoxide derivative in the body, causes any decrease, analogous to the action of epoxides, of hepatic glutathione (GSH) level in rats. Carbamazepine was administered to rats and liver GSH levels were determined spectrophotometrically. Neither a single low nor repeated low doses (30 mg/kg) of carbamazepine (CBZ) produced a statistically significant difference in GSH levels relative to controls. A single high dose of CBZ (100 mg/kg) produced a large and significant decrease relative to control (GSH level 3.82 +/- 0.64 vs 6.54 +/- 0.45 mumol GSH/g liver). CBZ and its metabolite carbamazepine-10,11-epoxide were determined in plasma by HPLC after the high dose of carbamazepine administration. The concentrations of carbamazepine and carbamazepine-10,11-epoxide were 18.9 +/- 2.9 micrograms/ml and 10.7 +/- 2.8 micrograms/ml, respectively.     

Primidone-carbamazepine interaction: clinical consequences

A 15-year old boy, suffering from partial complex seizures, was treated with primidone (PR) and carbamazepine (CBZ). In spite of daily doses in the usual range (PR = 12 mg/kg, CBZ = 30 mg/kg), he was not free from seizures and serum levels of CBZ were remarkably low (4.8 micrograms/ml). A good control of seizures was obtained after gradually stopping treatment with PR. This lead to a substantial increase of CBZ serum levels to a decrease of carbamazepine-10, 11-epoxide levels and a 60% reduction in total CBZ clearance.