卡马西平对白细胞及肾功能的影响

近年来,卡马西平(carba mazepine简称CBZ)。在神经精神科的应用日渐增多,临床报道认为,该药有一定的不良反应。我们于1987年3～9月对精神病人用CBZ治疗前后的白细胞及肾功能进行了观察研究,现报告如下。     

卡马西平的不良反应及使用时的注意事项

卡马西平(酰胺咪嗪 Carbamazepine CBZ)临床广泛用于癫痫、心率失常、尿崩症、三叉神经痛及耳鸣等症的治疗,但 CBZ 不论单用或联合用药均有严重的不良反应,甚至危及生命,值得高度重视。1 CBZ 的不良反应1.1 神经系统 CBZ 较常见的严重不良反应为神经毒作用,多发生在用药后1～2周,表现头痛、眩晕、嗜睡或烦燥不安、眼球震颤、不自主运动、共济失调、言语含糊、攻击行为、精神障碍及昏迷等。临床及     

卡马西平的不良反应

卡马西平(Carbamazepine,CBZ)常用于治疗癫痫、三叉神经痛、心律失常、躁狂症、肌张力异常及尿崩症等疾病,由于临床应用广泛,不良反应日渐增多,无论单独还是联合用药,其毒性反应均较为严重,本文就CBZ的不良反应作一概述. 1 CBZ的不良反应 1.1 神经系统[1～3 CBZ较常见的严重不良反应为神经毒作用,多发生在用药后1～2周,表现为头痛、头晕、乏力、烦躁不安或嗜睡、复视、眼球震颤、不自主运动、共济失调、语言含糊、精神障碍及昏迷等.当CBZ血总浓度>7.9μg/ml或游离CBZ>1.51μg/ml时可出现复视、眼球震颤.临床研究表明,CBZ可致运动和感觉传导速度进行下降.     

卡马西平不良反应114例分析

目的：探讨卡马西平(CBZ)所致药物不良反应(ADRs)的一般规律与特点。方法：对1995年1月～2002年12月国内医药期刊文献报道应用CBZ发生的ADRs进行统计分析。结果：CBZ所致的ADRs以皮肤及其附件损害最为常见，严重者可累及机体多个器官系统，甚至致死。结论：合理应用CBZ，重视ADRs的监测，确保用药安全。     

卡马西平致高钾血症1例

<正> 卡马西平(carbamazepine, CBZ)是目前广泛用于治疗癫痫发作和三叉神经痛的首选药物,并已证明对某些精神疾患有效。近10yr来的临床结果表明在用CBZ治疗过程中,至少有25％产生不良反应。但短期内应用CBZ引起高钾血症者,作者未见国内报道。现将我院遇到1例报道如下。 赵某,女,58yr。因三叉神经痛阵发性颊部闪     

卡马西平的不良反应

卡马西平(cavbamazepine,CBZ)为临床常用抗癫痫药,不良反应发生率为33%,与多种抗癫痫药联用时达47%,不良反应可累及全身各系统,有的较为严重甚至危及生命,现将CBZ较严重的不良反应概述如下。1　对神经系统的损害1.1　小脑及脑干功能障碍　慕小莉[1]报道1例73岁男患者,因三叉神经痛给予本品0.2g,tid,用药2次后患者精神萎糜,嗜睡,全身无力,手足颤抖,不易平衡,视物不清,情绪焦躁不安。停药1.5天后其症状基本消失,唯嗜睡持续6天后方恢复正常。1.2　红霉素诱发CBZ致神经系统损害　红霉素与CBZ的药物动力学相互作用具有临床意义,红霉素可导致…     

卡马西平致高敏反应综合征误诊为川崎病6例

卡马西平(CBZ)是常用抗癫药物，临床应用时易导致高敏反应。该文报道了6例患儿因服用CBZ 2～4周后出现高敏反应，临床表现为皮疹，持续性高热，口唇潮红伴皲裂，眼结膜充血，淋巴结肿大，肝脏损害，外周血白细胞增高。由于临床医师询问病史不详细，导致误诊为川崎病，后经停用CBZ，改用托吡酯，患儿好转。提示临床使用CBZ时应密切注意其不良反应。     

高剂量卡马西平中毒及其解救1例

卡马西平(carbamazepine,CBZ)主要用于治疗癫痫,三叉神经痛以及肌张力异常和尿崩症等疾病。过量服用CBZ 有生命危险,但临床少有报道。本文报告1例超剂量服用CBZ 后所致的毒性反应,并结合病例观察进行讨论。病例报告患者男性,22a,因故误服CBZ胶囊(上海第二十一制药厂,批号:881001)15粒,每粒200mg,2h 后感头昏、嗜睡,3h 后呼之不应,遂入我院急诊并予以3000ml 生理盐水     

托吡酯与卡马西平对照治疗成人癫痫133例

目的:比较托吡酯(TPM)及卡马西平(CBZ)单药治疗新诊断的部分性发作成人癫痫患者的疗效及耐受性.方法:133例患者入组,自愿选择进入TPM组58例和CBZ组75例.起始剂量TPM 25mg·d-1,nd,CBZ100mg·d-1,bid.根据患者的发作情况及是否发生不良反应调整剂量,并充分观察该剂量下的疗效及耐受性,以达最佳或最终剂量.通过比较两组患者治疗前后的月平均发作次数变化和因不良反应退出试验的病例比例评价药物的总体疗效.结果:观察时间TPM组(8.10±6.35)个月,CBZ组(15.69±10.23)个月.最佳或最终剂量范围TPM组50～300mg·d-1,CBZ组100～600mg·d.按照发作频率减少≥50%、无效或发作增加、因不良反应退出试验分级,两组比较差异有显著性,两组总有效率分别为75.9%及68.0%(P=0.033 6),因不良反应退出比例TPM组明显低于CBZ组(1.7%vs 14.7%).结论:TPM单药治疗成年新诊断部分性发作癫痫患者的疗效与CBZ相当,安全性和耐受性明显优于CBZ.     

卡马西平和苯妥英钠的血药浓度监测

卡马西平(CBZ)和苯妥英钠(DPH)是临床治疗癫痫的主要药物,应用较广泛。由于它们的治疗指数低,安全有效的血药浓度范围窄(CBZ的有效血药浓度范围为4～12μg/ml,DPH的有效血药浓度范围为10～20μg/ml),故对癫痫病人使用CBZ和DPH时进行常规的血药浓度监测,在临床上是十分有益的。作者曾对门诊16例癫痫病例进行CBZ和DPH血药浓度监测,取得一定效果。现报道如下。 一、血药浓度测定方法 仪器 KONTRON 322型HPLC仪,332型可变波     

冰片对卡马西平在家兔体内药代动力学的影响

目的观察冰片对卡马西平(carbam azep ine,CBZ)及10,11-环氧化卡马西平(10,11-epoxide carbam azep ine,ECBZ)在家兔体内药动学过程的影响。方法CBZ和冰片灌胃给药,高效液相法检测家兔血浆和脑脊液中CBZ及ECBZ的浓度,并计算药动学参数。结果冰片和CBZ合用可使CBZ的药动学参数T12(ka)、Tpeak、AUC增大而Ka和CL减少;ECBZ的药动学参数T12(ke)和Tpeak增大而Ke减少;ECBZ的脑血比提高。结论冰片可提高CBZ的生物利用度,减慢代谢,并促进血脑屏障对ECBZ的通透性。     

Carbamazepine levels in breast milk

The carbamazepine (CBZ) concentration of breast milk was determined in 19 epileptic patients of whom 13 were receiving CBZ monotherapy. Two lactation periods under CBZ monotherapy were followed in 2 of these 13 patients. The CBZ concentration of the breast milk was 36.4% of the maternal CBZ serum level (mean value). The correlation coefficient was 0.44; the regression line follows the equation y = 0.12X + 1.63. The CBZ concentration was measured in a total of 50 milk samples during the lactation period (cases of monotherapy plus combination therapy). The CBZ concentration ranged from 1 to 4.8 micrograms/ml (mean 2.5 micrograms/ml). The free CBZ concentration in the maternal serum was measured in four patients. The correlation between CBZ in the breast milk and free CBZ levels was 1.6 to 1.8. The ratio of carbamazepine-epoxide (ECBZ) in the milk to ECBZ determined in serum was 0.53. Continuing galactorrhea after delivery was observed in one patient. The CBZ and ECBZ levels determined 3.5 years after delivery were higher in the milk than in the serum. The observations of breast-fed and non-breast-fed children whose mothers were on CBZ monotherapy disclosed poor suckling in only 1 of 15 infants.     

Effect of ponsinomycin on single-dose kinetics and metabolism of carbamazepine

The effect of ponsinomycin (or miocamycin), a new macrolide antibiotic, was investigated on the pharmacokinetics of carbamazepine (CBZ) administered as a single dose in healthy volunteers. Disposition of the active 10,11 epoxycarbamazepine (ECBZ) was investigated as well. For each compound both total and free plasma concentrations were measured. A moderate (+13%) but statistically significant (p less than 0.05) increase of CBZ total area under the curve (AUC), was observed in the presence of ponsinomycin, accompanied by a 26% decrease (p less than 0.01) in the AUC of its metabolite. There was a tendency toward an increase in AUC of unbound CBZ, although it was not statistically significant. Together these data suggest that formation of ECBZ is inhibited in the presence of ponsinomycin. The relative importance of the epoxy-diol metabolic pathway being increased at steady state due to autoinduction, results of this study suggest that CBZ plasma levels should be carefully monitored in patients receiving ponsinomycin.     

Time-dependent influence of pentoxifylline on the pharmacokinetics of orally administered carbamazepine in human subjects.

The time-dependent influence of pentoxifylline (PTX) on the pharmacokinetics of carbamazepine (CBZ) was studied after single-dose oral administration of 100 mg CBZ either alone or in combination with 400 mg PTX at 10:00 and 22:00 h. Serum samples were collected at predetermined time intervals and analysed for unchanged CBZ using high-performance liquid chromatography. The pharmacokinetic parameters of CBZ were calculated using the model-independent method. PTX reduced the rate (Tmax, 8.58 +/- 2.64 vs 5.66 +/- 1.44 h; K(a); 0.47 +/- 0.14 vs 0.72 +/- 0.19 h(-1)), but not the extent of CBZ absorption at 22:00 h treatment. However, such a change was not observed for 10:00 h treatment. No significant changes were observed in other pharmacokinetic parameters of CBZ under the influence of PTX for both 10:00 h as well as 22:00 h treatments. The clinical significance of the time-dependent influence of PTX on the rate of absorption of CBZ will be revealed upon extension of the study to patients.     

Monotherapy with conventional and controlled-release carbamazepine: a double-blind, double-dummy comparison in epileptic patients.

1. Twenty-one epileptic patients completed a double-blind, double-dummy, random order, crossover comparison of conventional carbamazepine (CBZ, Tegretol, Ciba-Geigy) with a new controlled-release formulation (CBZ-CR, Tegretol Retard). All participants were stabilised on maximally tolerated doses of CBZ as monotherapy (one twice daily, twelve three times daily, eight four times daily). Each preparation was taken with a matched placebo of the other for 4 weeks. 2. Peak serum CBZ concentrations (mean +/- s.e. mean) were lower (CBZ 11.4 +/- 0.4 mg l-1; CBZ-CR 10.4 +/- 0.5 mg l-1; P less than 0.01) and times to peak longer (CBZ 3.6 +/- 0.5 h, CBZ-CR 5.2 +/- 0.7 h, P less than 0.01) during CBZ-CR treatment. Mean CBZ concentrations, however, were also slightly reduced with the new formulation (CBZ 9.9 +/- 0.3 mg l-1; CBZ-CR 9.1 +/- 0.5 mg l-1, P less than 0.05) and this was associated with greater seizure frequency (CBZ 2.8 +/- 1.2, CBZ-CR 3.8 +/- 0.9; P less than 0.05) during the CBZ-CR treatment phase. 3. Diurnal fluctuations (CBZ 41 +/- 3%, CBZ-CR 28 +/- 2%, P less than 0.01) and variations (CBZ 53 +/- 5%, CBZ-CR 33 +/- 3%; P less than 0.01) in serum CBZ concentration were substantially less with CBZ-CR and were similar to those calculated during a 6 or 8 hourly dosage interval with conventional CBZ (fluctuation 33 +/- 3%, variation 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

HPLC法测定血清中卡马西平、苯妥英和苯巴比妥浓度

采用反相高效液相色谱法同时测定血清中卡马西平、苯妥英和苯巴比妥的浓度，以非那西丁为内标，检测波长为210nm，流动相为甲醇：10mmol／L磷酸二氢钾溶液（58：42），其平均回收率分别为90．4％95．6％和94．1％。     

Dual effects of carbamazepine-phenytoin interaction

By intrapatient comparison at constant phenytoin (PHT) dose, the effect of increased carbamazepine (CBZ) dose was studied in 32 epileptic outpatients treated with a combination of PHT and CBZ. The mean PHT plasma concentration, as well as the concentration/dose ratio for PHT, became significantly higher secondary to increased doses of CBZ (14.1 +/- 3.5 vs. 19.3 +/- 3.6 micrograms/ml and 2.8 +/- 1.0 vs. 3.9 +/- 1.4 micrograms/ml plasma per milligram/kilogram daily dose, respectively; p less than 0.001). Concomitantly, in spite of CBZ dose higher by 17.6%, the CBZ concentration increased by only 6.4%, and the CBZ concentration/dose ratio actually decreased by 10%. In contrast, by intrapatient comparison at constant CBZ dose, the effect of reduced PHT dose on CBZ was studied in 22 patients. The mean CBZ plasma concentration as well as the concentration/dose ratio for CBZ appeared significantly higher, with a concomitant reduction of PHT (6.7 +/- 1.6 vs. 8.6 +/- 1.6 micrograms/ml and 0.37 +/- 0.1 vs. 0.49 +/- 0.2 micrograms/ml plasma per milligram/kilogram daily dose, respectively; p less than 0.001). This simultaneous dual effect--inhibition of PHT metabolism by CBZ and induction of CBZ metabolism by PHT--can result in PHT intoxication along with a fall in CBZ plasma concentration to a subtherapeutic range. This effect may be avoided or reduced if the PHT concentration is adjusted to approximately 13 micrograms/ml before CBZ is added or increased.     

反相高效液相色谱法同时测定苯妥英钠、卡马西平的血药浓度

目的建立反相高效液相色谱法同时测定苯妥英钠、卡马西平的血药浓度。方法采用C18柱（200mm×4．6mm，5μm），甲醇-水（48：52）为流动相，紫外检测波长为205nm，流速1．1mL／min，柱温40℃。结果两种药物分离良好，苯妥英钠、卡马西平质量浓度线性范围分别为2．14～42．8μg／mL和2．04～20．40μg／mL，方法回收率分别为99．33％和99．64％，提取回收率分别为97，13％和96．64％，日内、日间RSD均小于4％．结论该方法操作简便、快速、准确，可用于临床治疗药物的监测。     

Measurement of carbamazepine and its main biotransformation products in plasma by HPLC.

We present a method that permits the simultaneous analysis of carbamazepine (CBZ) and its major biotransformation products, carbamazepine-10,11-epoxide (CBZ-E) and carbamazepine-10,11-dihydroxide (CBZ-diOH), in plasma samples. The method consists of plasma extraction in alkaline medium with NaCl added using chloroform-ethyl acetate (1:1, v/v) and later purification with n-hexane. The samples were submitted to reversed-phase chromatography (RP-18) using acetonitrile-water (3:7, v/v) as the mobile phase and detection at 220 nm. Recoveries of 62.0, 99.9, and 105.4% were obtained for CBZ-diOH, CBZ-E, and CBZ, respectively, with sensitivities of 0.32 micrograms/mL for CBZ-E and CBZ-dOH and of 0.64 micrograms/mL for CBZ. The method proved to be specific, thus permitting measurements in situations of drug combinations.     

高效液相色谱法测定苯巴比妥、苯妥英、卡马西平的血药浓度

目的 :建立 HPL C法测定抗癫药苯巴比妥 (PB)、苯妥英 (PT)、卡马西平 (CBZ)的血药浓度。方法 :反相柱 ODS- Hy-persil(4.6 m m× 10 0 mm ,5︼m ) ,流动相为甲醇∶水 (5 2∶ 48) ,流速 0 .8m l/ m in,紫外检测波长 2 5 4nm ,以上 3药互为内标。标本经 CH2 Cl2 提取 ,蒸干后用流动相重溶进样。结果 :PB、PT、CBZ的保留时间分别为 3.2 2、5 .5 7、6 .80 m in;最低检测浓度分别为 0 .2 5、0 .5、0 .0 5︼g/ m l;线性范围分别为 2 .5～ 40、2 .5～ 40、1.2 5～ 2 0︼g/ ml;相对回收率分别为 10 1.49%、10 4.19%、98.70 % ;日内 RSD分别为 1.81%、5 .94%、1.81% ;日间 RSD分别为 6 .0 6 %、3.35 %、3.96 %。结论 :本法具快速、灵敏、实用等优点。