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.     

HPLC法同时测定血清中苯妥英,卡马西平的浓度

本实验建立了用反相HPLC 法同时测定人血清中苯妥英及卡马西平的方法。以苯乙酮为内标,采用Ultrasphere ODS 柱(5μm)(φ4.6×150mm),甲醇:水(50:50)为流动相流速0.8ml/min 紫外210nm 检测,血清处理用于乙腈沉淀蛋白,样品预处理过程快速简便,整个过程仅需20min 即可检出。苯妥英最低检测浓度为0.626μg/ml,相对回收率为99.66～102.40%线性范围为1.252～40.06μg/ml,相关系数r=0.9999:卡马西平最低检测浓度为0.5μg/ml,相对回收率为101.28～103.93%,线性范围为1.274～20.38μg/ml,相关系数r=0.9999。将本法应用于临床治疗药物监测获得满意效果。     

卡马西平与其代谢物的抗癫痫和毒副反应

卡马西平体内代谢大致有4条途径,其中最重要的是通过10,11位环氧化,形成10,11-二羟卡马西平。卡马西平血浓度与疗效、毒副反应相关。它的代谢产物之一、环氧化卡马西平已在动物及临床实验中证明有抗惊厥活性。另外,它在体内蓄积过多,也是产生毒副反应的一个重要因素。有关环氧化卡马西平与疗效和毒副反应的关系正在深入研究中。     

用高效液相色谱法测定血清卡马西平及其代谢产物浓度

本文报告了一个可同时测定卡马西平及其少在40mg·L~(-1)内呈线性,1O,11一环氧卡马西平活性代谢产物血药浓度的高效液相色谱法。于至少在20mg·L~(-1)内呈线性。0.3ml血清样本中加入内标物(10—甲氧卡马西平)后.经4mol·L~(-1)氢氧化钠碱化.用二氯甲烷提取;提取液在室温中氮气流下挥干、流动相重组进样.进行色谱分析。以乙腈/甲醇/水(50/210/260.V/V)为流动相.以C_(18)反相桂(150×4.6mm)为固定相,检测波长为214nm。本法卡马西平及1O,11—环氧卡马西平的最小检出浓度分别为0.08mg·L~(-1)和0.1mg·L~(-1).平均绝对回收率分别为96.0％和97.3％;日内变异系数为3.3％～5.7%.日间变异系数为4.3％～9.0％;卡马西平至     

LC-MS/MS法同时测定人血清中卡马西平和拉莫三嗪浓度

目的:建立同时测定人血清中卡马西平和拉莫三嗪浓度的方法。方法:采用液-质联用法,以伐地那非和红地那非为内标,血清经乙腈直接沉淀后进样分析。色谱柱为XbridgeTMPhenyl,流动相为含0.02%甲酸的水溶液-含0.02%甲酸的乙腈溶液(60∶40),流速为0.3mL·min-1。电喷雾离子源,正离子多反应监测扫描分析,卡马西平和内标伐地那非的离子对分别为m/z237→194和m/z489→72;拉莫三嗪和内标红地那非的离子对分别为m/z256→43和m/z467→111。结果:卡马西平和拉莫三嗪血药浓度分别在5～500μg·L-1(r=0.9988)和100～10000μg·L-1(r=0.9964)范围内线性关系良好,定量下限分别为5、100μg·L-1。日内、日间RSD均<8%;平均提取回收率分别在88.9%～100.9%和89.5%～100.3%范围内。结论:本方法样品处理简便,适用于临床血药浓度监测及药动学研究。     

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。     

HPLC同时测定血清中苯妥英、苯巴比妥和卡马西平的浓度

目的 :建立同时测定微量血清中苯妥英、苯巴比妥和卡马西平浓度的方法。方法 :采用HPLC法 ,以巴比妥为内标同时测定。KromasilC18不锈钢色谱柱 ,流动相为甲醇 水 (5 7∶43) ,流速 0 .8ml·min 1,检测波长 2 5 4nm。结果 :检测浓度范围苯妥英为 4.0～ 5 0 .0 μg·ml 1(r=0 .9995 ) ,苯巴比妥 5 .0～ 6 0 .0 μg·ml 1(r =0 .9996 ) ,卡马西平为2 .5～ 2 0 .0 μg·ml 1(r =0 .9992 )。最低检测限分别为 1.0 μg·ml 1、2 .0 μg·ml 1和 0 .5 μg·ml 1;平均回收率分别为99.2 2 %、99.6 8%和 98.6 2 % ;日内和日间RSD均低于 5 % (n =5 )。结论 :该法准确、灵敏度高 ,重复性好 ,可作为 3种血药浓度监测的常规方法     

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.     

卡马西平血药浓度与抗癫痫作用及不良反应的关系

目的:了解卡马西平血药浓度与抗癫痫作用及不良反应的关系。方法:采用荧光偏振免疫法测定52例癫痫患者卡马西平的血药浓度。结果:31例血药浓度在4～12μg·mL~(-1),抗癫痫作用有效为25例,有效率约80.6％;17例血药浓度低于4μg·mL~(-1),无1例有效;4例血药浓度高于12μg·mL~(-1),全部有效但发生了明显的不良反应。结论:卡马西平疗效及不良反应与血药浓度有关。     

高效液相色谱法同时测定苯巴比妥、苯妥英、卡马西平的血药浓度

目的:建立以高效液相色谱法同时测定苯巴比妥、苯妥英、卡马西平血药浓度的方法。方法:取患者血清,经二氯甲烷提取后在C18柱上分析,流动相为甲醇-水(57:43),柱温为30℃,检测波长为254nm,流速为0.8ml/min。结果:苯巴比妥、苯妥英、卡马西平分别在2.5-40、2.5-40、1.25-20μg/ml范围内线性关系良好,日内和日间RSD<10％(n=5)。结论:本方法简便、稳定,用于苯巴比妥、苯妥英、卡马西平的血药浓度监测效果良好。     

Carbamazepine is not a substrate for P-glycoprotein

AIMS: To determine whether the anticonvulsant carbamazepine (CBZ), a known CYP3A4 substrate, is also a substrate for the multidrug efflux transporter P-glycoprotein (Pgp). METHODS: The role of Pgp in the transport of CBZ was assessed in three systems: (a) in mdr1a/1b(-/-) and wild-type mice after administration of 2 mg kg-1 and 20 mg kg-1, which served as a model for brain penetration; (b) in Caco-2 cells, an in vitro model of the intestinal epithelium that is known to express high Pgp levels; and (c) by flow cytometry in lymphocytes using rhodamine 123, a fluorescent substrate for PgP. RESULTS: Brain penetration of both doses of CBZ at 1 h and 4 h was comparable in wild-type and mdr1a/1b(-/-) mice. Transport across the Caco-2 cell monolayer was Pgp-independent, and was not affected by the Pgp inhibitor PSC-833. CBZ had no effect on rhodamine 123 efflux from lymphocytes, in contrast to verapamil, which increased fluorescence intensity fivefold. CONCLUSION: CBZ is not a substrate for Pgp. Its efficacy is unlikely to be affected by Pgp over-expression in the brain. Furthermore, the interaction of CBZ with drugs that modulate both CYP3A4 and Pgp function such as verapamil is probably due to inhibition of CYP3A4 and not Pgp.     

140例癫痫患儿卡马西平血药浓度结果分析

目的通过检测癫痫患儿血清卡马西平（CBZ）浓度,探讨影响其浓度的因素,为临床个体化给药方案提供依据。方法采用高效液相色谱法（HPLC）测定癫痫患儿血清CBZ浓度,并结合临床疗效进行分析。结果140例癫痫患儿中血清CBZ浓度〈4 mg.L-1的有25例,其中控制＋有效为10例;血清CBZ浓度〉12 mg.L-1的有7例,其中1例无效;血清CBZ浓度在4~12 mg.L-1间的有108例,其中控制＋有效为97例。结论癫痫患儿血清CBZ浓度受年龄、个体差异、药物相互作用等因素的影响,常规监测其浓度,对确保安全、有效、合理使用抗癫痫药物具有十分重要的意义。     

Carbamazepine intoxication in alcohol dependent epileptic patients

Carbamazepine is frequently administrated to alcohol addict patients. The aim of this study was to evaluate the influence of alcohol addiction on carbamazepine pharmacokinetics and severity of drug intoxication. The total of 158 carbamazepine intoxicated patients participated in the study (76 non-alcohol-dependent, and 82 alcohol-dependent subjects). The results of the study indicate that the level of unconsciousness depends on carbamazepine concentration. The frequency of anticholinergic toxidrome was higher in alcohol-dependent patients (88.6% – alcohol-abused subjects, and 78.3% – alcoholics in abstinency) comparing to non-alcohol-dependent epileptics (67.1%). The average biological half-life of carbamazepine in non-addicted epileptics was 41.5 h, 43.5 h for alcohol-dependent patients during abstinency, and 38.6 in abused patients. It may be concluded that ethanol doesn't influence the pharmacokinetic and pharmacodynamic of carbamazepine in acute drug intoxication.     

紫外分光光度法测定癫痫患者的卡马西平血药浓度

目的探讨癫痫患者卡马西平血药浓度的测定方法。方法采用紫外分光光度法测定卡马西平的血药浓度。结果卡马西平质量浓度线性范围是2～10μg/mL,r=0.9996。测定的71例患者血药浓度在2.43～10.42μg/mL范围内。结论所用方法简便、快速、实用,适合于各级医院、社区卫生服务中心开展卡马西平的治疗药物监测,有助于指导临床合理用药。     

高效液相色谱法测定人血清中卡马西平浓度及其临床应用

本文建立了高效液相色谱法测定人血清中卡马西平浓度，以μＢｏｎｄａｐａｋＣ１８（１０ｍｍ）为固定相，甲醇－乙腈－水（４５：１０：４５）为流动相，硝基安定为内标，检测波长为２５４ｎｍ。方法最低检测限为２．５ｎｇ（Ｎ／Ｓ＝３），血清中最低检测浓度为０．２５ｍｇ／Ｌ，卡马西平血清浓度在２～１４ｍｇ／Ｌ范围内线性关系良好（γ＝０．９９９７），方法回收率为９９．的％，不同浓度水平测定结果的日内变异系数＜３．２％，日间变异系数＜６．２％。方法操作简便、快速，尤宜常规应用。临床应用结果满意。     

高效液相色谱法测定人血浆中卡马西平血药浓度

目的建立一种快速、方便、准确的方法测定卡马西平血药浓度。方法用RP-HPLC法测定卡马西平血药浓度。结果线性范围0.4-25μg/ml,最低检测浓度0.15μg/ml,最低定量浓度0.4μg/ml,回归方程Y=12.5X+0.1425(r=0.9960)。回收率为97.5%,日内和日间精密度分别为RSD=1.5%和RSD=2.3%。结论本法准确、快速,适合临床上血药浓度检测。     

反相高效液相色谱法同时测定人血清中地尔硫卓及卡马西平浓度

本文采用反相高效液相色谱法，以安定为内标，同时测定血清中卡巴西平（ＣＢＺ）和地尔硫卓（ＣＺ）的浓度。用Ｗａｔｅｒｓ产μ－Ｂｏｎｄａｐａｋ Ｃ１８色谱柱，甲醇－ｐＨ为６．８４的磷酸盐缓冲（内含０．０４％二乙胺）＝７０：３０（ｖ／ｖ）为流动相，紫外检测波长为２３７ｎｍ。ＣＢＺ两种浓度（５、１０μｇ／ｍｌ）的平均回收率及其日内精密ＲＳＤ分别为１０１．３％、１０１．８％及０．７％、１．１％。ＤＺ两种浓度（     

口服卡马西平出现发热1例

卡马西平(carbamazepine)为抗癫痫药,也可用于治疗神经痛[1],是神经科常用药物.虽此药有较多不良反应[2],但单纯致发热者罕见报道.笔者曾报道1例因卡马西平致发热和淋巴结肿大[3],而本例仅为发热.现报道如下.     

Population Pharmacokinetic Modeling of Steady State Carbamazepine Clearance in Children, Adolescents, and Adults

Carbamazepine (CBZ) clearance decreases from childhood to adulthood and the factors determining this change could include age, size, autoinduction, or maturational changes. This study aims to describe the population pharmacokinetics of CBZ in children and young adults and test the hypothesis that CBZ clearance correlates with weight, surface area, and age. CBZ therapeutic drug monitoring data (sparse data) were collected from child and adult epileptics, and rich data were obtained from a bioequivalence study of CBZ in young adults. Population pharmacokinetic analysis was performed using NONMEM V. Forward stepwise, multiple regression was performed on the covariates. Bootstrap validation was performed. A total of 946 observations from 91 subjects, ages 0.7–37 years, were collected and analyzed. A one-compartment, first-order absorption and elimination model, with exponential interindividual error and additive residual error models was developed. The population model was: Clearance (Lhr ^–1)=((2.24 · Surface area (m ²))+(0.047 · Dose (mg · kg ^–1)); Volume of distribution (L)=0.37 · weight (kg); Absorption rate constant=0.013 (hr ^–1). CBZ clearance increased with surface area and dose.     

Carbamazepine differentially affects the pharmacokinetics of fexofenadine enantiomers

AIM

This aim of this study was to characterize the impact of the P-glycoprotein (P-gp) inducer, carbamazepine, on fexofenadine enantiomer pharmacokinetics.

METHODS

Twelve healthy volunteers initially received a 60 mg dose of fexofenadine alone. Subsequently, a 100 mg dose of carbamazepine was administered three times daily (300 mg day⁻¹), and on day 7, fexofenadine was co-administered.

RESULTS

Carbamazepine significantly decreased the area under the plasma concentration–time curve and the amount excreted into the urine of (S)- and (R)-fexofenadine. The P-gp inducer showed a greater effect on the pharmacokinetic parameters of (S)-fexofenadine.

CONCLUSION

This study indicates that carbamazepine may alter the pharmacokinetics of fexofenadine enantiomers.