桔梗对卡马西平家兔体内血药浓度的影响

目的:为了探讨患者用药时中药与西药之间可能发生的相互作用,主要研究中药桔梗对神经系统药物卡马西平血药浓度的影响.方法:用HPLC仪测定卡马西平单独给药、桔梗与卡马西平合并给药(给桔梗1次及给桔梗7次)后家兔体内的血药浓度,做药-时曲线,进行统计学检验.结果:合用桔梗组在给药后6 h卡马西平血药浓度明显高于单用卡马西平组,曲线下面积也高于单用卡马西平组.桔梗给药7次后卡马西平在2 h、4 h、6 h的血药浓度高于给桔梗1次,存在显著性差异(P＜0.05).结论:由于桔梗可以增加卡马西平血药浓度,在应用卡马西平时加用桔梗,可以减少卡马西平的用量,在保持疗效不变的情况下减少不良反应.本研究对于临床安全、合理用药有很强的指导意义.     

卡马西平血药浓度监测7例及其分析

目的监测并分析卡马西平的血药浓度,合理使用卡马西平。方法使用全自动发光免疫分析仪测定卡马西平的血药浓度,对卡马西平血药浓度与疗效的关系及影响卡马西平血药浓度的因素进行分析。结果7例应用卡马西平患者,共测定12次血药浓度,其中6例在有效血药浓度范围内,其余6例低于有效血药浓度4 mg/L。结论临床使用卡马西平应进行血药浓度监测,并结合患者的生理、病理、药动学、药物相互作用及临床疗效,保证个体化给药。     

护肝宁片对卡马西平在大鼠体内药物动力学的影响

探讨了护肝宁片对卡马西平在大鼠体内药物动力学的影响.大鼠随机分为生理盐水对照组和护肝宁片给药组.护肝宁片连续给药10d后,灌胃给予卡马西平(50mg/kg),用HPLC法测定卡马西平的血药浓度.采用非隔室模型分析方法计算卡马西平的药物动力学参数.单用卡马西平及与护肝宁片合用后,两组的Ke、t1/2、CL、cmax、tmax无显著性差异(P>0.05),而AUC则有显著性差异(P<0.05).结果表明,口服护肝宁片可降低卡马西平的吸收,但不影响卡马西平的体内代谢.     

丙戊酸钠对卡马西平药代动力学的影响

目的:考察丙戊酸钠对卡马西平药代动力学的影响。方法:6名健康志愿者分别口服单剂量卡马西平片以及卡马西平和丙戊酸钠片,采用荧光偏振免疫法测定卡马西平血药浓度,经3p97程序处理,计算卡马西平的药代动力学参数以及丙戊酸钠对卡马西平药代动力学参数的影响。结果:合用丙戊酸钠后,卡马西平的Ke,CL/F明显增加,而T_(1/2Ke),AUC_(0-t)明显减小(P<0.05)。结论:丙戊酸钠可加速卡马西平的排泄,使卡马西平的半衰期缩短,生物利用度减小。     

118例癫痫患者卡马西平血药浓度监测结果及影响因素分析

目的 探讨癫痫患者卡马西平（CBZ）血药浓度的影响因素,为临床合理使用提供依据。方法 选取118例规律服用卡马西平治疗的癫痫患者作为研究对象,采用高效液相色谱法（HPLC）进行血药浓度监测,分析影响卡马西平血药浓度的因素。结果 75.42%的患者服用卡马西平后血药浓度控制在4~12 μg·mL^-1之间;性别因素、年龄因素对卡马西平血药浓度的影响不明显（P＞0.05）;联合其他抗癫痫药时,无效浓度比例较高,具有统计学差异(P＜0.05)。结论 服用卡马西平后,患者卡马西平血药浓度的个体差异大,尤其是合并使用其他癫痫药者。因此应避免联合使用,并积极监测患者药物浓度,实施个体化给药,促进安全合理使用。     

丙戊酸钠对卡马西平药代动力学的影响

目的：考察丙戊酸钠对卡马西平药代动力学的影响。方法：6名健康志愿分别口服单剂量卡马西平片以及卡马西平和丙戊酸钠片，采用荧光偏振免疫法测定卡马西平血药浓度，经3p97程序处理，计算卡马西平的药代动力学参数以及丙戊酸钠对卡马西平药代动力学参数的影响。结果：合用丙戊酸钠后，卡马西平的Ke,CL/F明显增加，而T1/2Ke,AUC0-1明显减小（P＜0．05）。结论：丙戊酸钠可加速卡马西平的排泄，使卡马西平的半衰期缩短，生物利用度减小。     

卡马西平血药浓度监测及联合用药

目的 分析卡马西平治疗癫痫血药浓度与剂量关系。方法 用荧光偏振免疫法(FPIA)对不同年龄的200例癫痫患者进行卡马西平血药浓度监测,并结合临床分析比较。结果 卡马西平稳态血药浓度与给药剂量、给药时间密切相关。结论 卡马西平血药浓度监测有着重要意义。     

卡马西平血药浓度监测及联合用药

目的分析卡马西平治疗癫痫血药浓度与剂量关系.方法用荧光偏振免疫法(FPI A)对不同年龄的2 00例癫痫患者进行卡马西平血药浓度监测,并结合临床分析比较.结果卡马西平稳态血药浓度与给药剂量、给药时间密切相关.结论卡马西平血药浓度监测有着重要意义.     

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。     

儿童癫痫患者CYP酶活性与血清卡马西平浓度和临床疗效的相关性分析

目的 探讨癫痫患儿CYP3A的活性与服用卡马西平后的血药浓度和临床疗效的关系. 方法 以高效液相色谱（HPLC）法测定尿液中氢化可的松（HC）与6β-羟基氢化可的松（6β-OHC）的含量,以6β-OHC/HC来评估CYP3A酶活性（CA）. 采用荧光偏振免疫分析法测定儿童血清卡马西平浓度,进行CYP3A活性与卡马西平后血清浓度、临床疗效的相关性分析. 结果 CA常用对数（lgCA）与卡马西平血药浓度线性相关,r＝ 0.846. 不同临床疗效治疗组患者的CA值差异有显著性（P＜0.05）. 结论 CYP3A活性可用于预测卡马西平血药浓度和临床疗效,指导个体化给药.     

桔梗水提液的镇咳、祛痰作用研究

目的:研究桔梗水提液的镇咳、祛痰作用。方法:通过氨水引咳,观察小鼠咳嗽潜伏期和咳嗽次数,实验分为5组,即模型(等容生理盐水)、右美沙芬(0.03g·kg-1)和桔梗水提液高、中、低剂量(16、8、4g·kg-1)组,ig给药,每12h1次,连续6次。通过测定小鼠气管酚红排泌量来评定小鼠气管黏液分泌量,实验分为5组,即空白对照(等容生理盐水)、盐酸氨溴索(0.03g·kg-1)和桔梗水提液高、中、低剂量(16、8、4g·kg-1)组,ig给药,每12h1次,连续6次。结果:与模型组比较,桔梗水提液高、中剂量组咳嗽潜伏期显著延长(P<0.01或P<0.05),咳嗽次数显著减少(P<0.01或P<0.05)。与空白对照组比较,桔梗水提液高、中剂量组小鼠气管酚红排泌量显著增加(P<0.01或P<0.05)。结论:桔梗水提液在镇咳、祛痰方面效果较好,本研究可为临床用药提供理论依据。     

393例抗癫痫药物血药浓度监测结果分析

目的通过分析该院抗癫痫药物血药浓度监测分析的结果,为临床合理用药提供参考。方法运用高效液相色谱法,对丙戊酸钠、苯妥英钠、卡马西平、苯巴比妥在393例病人中的血药浓度进行测定,并对结果进行统计分析。结果丙戊酸钠(50～100 mg.L-1)、卡马西平(4～12 mg.L-1)、苯妥英钠(10～20 mg.L-1)、苯巴比妥(15～40 mg.L-1)在有效血药浓度范围内的例数分别为:111例(76.55%)9、3例(77.50%)、41例(73.21%)、52例(72.22%)。结论抗癫痫药物血药浓度监测结果显示,临床用药应综合考虑各方面因素,实施个体化给药方案,确保用药安全有效。     

Effect of nimodipine, a dihydropyridine calcium channel antagonist on the pharmacokinetics of carbamazepine in rhesus monkeys

Calcium channel antagonists have been shown to have an anticonvulsant activity in a variety of seizure models and also to potentiate the anticonvulsant activity of other standard antiepileptic drugs like carbamazepine, phenytoin and valporoate. A pharmacokinetic interaction may be involved in such potentiation. This cross over single dose study was carried out to find out if there was a pharmacokinetic interaction between carbamazepine, a commonly used antiepileptic drug and nimodipine, a dihydropyridine calcium channel antagonist in rhesus moneys. Carbamazepine 46 mg/kg and nimodipine 9.6 mg/kg was administered through a nasogastric tube and blood samples were collected at 0.5, 1, 2, 3, 6, 9, 12, 24, 48, 72 and 96 hours after drug administration and were assayed for carbamazepine. Nimodipine caused a significant increase in peak plasma concentration (C(max)) of carbamazepine and a decrease in plasma absorption half life (t1/2 alpha). There was no significant change in other pharmacokinetic parameters between the two groups. The results of the study suggest that concurrent administration of carbamazepine and nimodipine may cause a significant rise in carbamazepine concentration as may contribute to a potentiation of anticonvulsant effect of carbamazepine and an increase in the incidence of adverse effects warranting that nimodipine should be prescribed cautiously in epileptic patients receiving carbamazepine and it might be very appropriate to do therapeutic drug monitoring of carbamazepine in such patients.     

Lack of effect of citalopram on the steady-state pharmacokinetics of carbamazepine in healthy male subjects

Carbamazepine, a drug used in the treatment of seizure disorders, and citalopram, a highly selective serotonin reuptake inhibitor used for the treatment of depression and other psychiatric disorders, are both metabolized predominantly by the cytochrome P4503A4 isozyme. In this study, the effect of subchronic administration of citalopram on the steady-state pharmacokinetics of carbamazepine was evaluated in 12 healthy male subjects. Carbamazepine was administered orally twice daily as a 100-mg dose from days 1 to 3, as a 200-mg dose twice a day from days 4 to 6, and as a 400-mg dose once a day from days 7 to 35. Citalopram, 40 mg, administered once daily, was added to the carbamazepine-dosing regimen on days 22 to 35. The steady-state plasma concentration profiles of carbamazepine and its active metabolite, carbamazepine 10,11-epoxide, on day 35 (in the presence of steady-state levels of citalopram) were compared to the corresponding carbamazepine and epoxide metabolite profiles on day 21 (in the absence of citalopram). No significant differences were found between mean steady-state values for maximal drug concentration, area under the curve, or time of maximal concentration values for carbamazepine and its epoxide metabolite before and after the addition of citalopram to the daily carbamazepine dosing regimen (p > 0.05). These results suggest that the use of citalopram in patients stabilized on carbamazepine should not produce clinically significant changes in carbamazepine plasma concentrations.     

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。     

天王补心丸全方及方中缺桔梗对小鼠镇静催眠作用的影响

目的:探讨中药古方天王补心丸对小鼠中枢神经系统的药理影响及舟楫之剂桔梗在该方剂中的作用.方法:采用小鼠自发活动计数、延长戊巴比妥钠睡眠时间及抗惊厥试验等方法,观察天王补心丸方、缺桔梗的天王补心丸方、天王补心丸中臣药酸枣仁、酸枣仁与桔梗配伍及其桔梗单独使用时的镇静、催眠与抗惊厥作用.结果:天王补心丸有良好的镇静、催眠与抗惊厥作用,但该方去掉桔梗后,镇静、催眠与抗惊厥效果明显下降;天王补心丸中重要成分酸枣仁本身有较好的镇静催眠作用加上桔梗后效果得到加强,但不如天王补心丸全方,桔梗本身没有镇静、催眠与抗惊厥作用.结论:在天王补心丸方剂的配伍中,桔梗作为舟楫之剂确实能载药上浮,增强该方对中枢神经系统的作用.     

Pharmacokinetic interaction between efavirenz and carbamazepine after multiple-dose administration in healthy subjects

The effect of efavirenz on the pharmacokinetics of carbamazepine and vice versa was investigated in adult healthy subjects in a randomized, open-label, 2-period crossover, multiple-dose study. Subjects were randomized to receive either efavirenz 600 mg qd for 14 days or carbamazepine titrated to 400 mg qd for 21 days followed with both drugs for another 21 or 14 days. The pharmacokinetics was evaluated for efavirenz, carbamazepine, and the major metabolite of carbamazepine, carbamazepine-10,11-epoxide. Coadministration of carbamazepine with efavirenz significantly reduced the exposure of efavirenz (geometric mean ratios [90% confidence interval]: area of plasma concentration-time curve during the dosing interval of 24 hours [AUCtau], 0.64 [0.60-0.68]; maximum plasma concentration [C(max)], 0.79 [0.74, 0.85]) and carbamazepine (AUC(tau), 0.73 [0.67-0.80]; C(max), 0.80 [0.76, 0.85]) but had minimal impact on the exposure of carbamazepine-10,11-epoxide (AUC(tau), 0.99 [0.85-1.15]; C(max), 1.05 [0.91, 1.22]). In summary, a 2-way pharmacokinetic interaction between efavirenz and carbamazepine was demonstrated in this study.     

抗癫痫中成药中非法添加西药成分的血药浓度监测分析

目的：对长期服用抗癫痫中成药的患者进行血药浓度监测,查明抗癫痫中成药中非法添加的西药成分。方法：通过全自动生化分析仪,采用酶联免疫法测定中成药中添加的丙戊酸、卡马西平、苯巴比妥、苯妥英的种类及血药浓度。结果：所有服用抗癫痫中成药的患者中均检测到上述四种西药成分,其中含丙戊酸17例,血药浓度在有效范围内占23.53%;含卡马西平17例,血药浓度在有效范围内占17.65%;含苯巴比妥17例,血药浓度在有效范围内占41.18%;含苯妥英5例,血药浓度在有效范围内占60.00%。结论：本方法操作简便、准确,可快速筛查抗癫痫中成药中非法添加的西药成分,便于临床指导患者合理用药。     

Impairment of psychomotor function at modest plasma concentrations of carbamazepine after administration of the liquid suspension to naive subjects.

1. The influence of pharmaceutical formulation on the plasma drug concentration-time curve and the psychomotor responses to 400 mg carbamazepine has been assessed in 12 healthy male volunteers; three formulations and placebo were compared in a randomised, blind, crossover study. 2. The plasma concentration of carbamazepine rose to a maximum of 3-7 mg l-1 by 2-3 h after administration of the liquid suspension. Conventional and controlled release tablet formulations gave lower peaks at about 8 and 32 h, respectively. From 32 h onwards the plasma concentrations from the three formulations were indistinguishable. 3. Significant impairment of psychomotor function was observed after the liquid suspension only; subjective sedation was significant at 1 and 2 h and the critical flicker fusion frequency threshold was lowered at 1-8 h. Digit-symbol substitution, choice reaction time and body sway gave less conclusive evidence of impairment. 4. The results do not support the hypothesis that a psychomotor effect from carbamazepine is a threshold phenomenon with a critical plasma drug concentration at about 8 mg l-1. 5. A second hypothesis that rate of rise of plasma carbamazepine concentration has an important influence on psychomotor effect fits the observations. This interpretation is tentative since the use of a fixed dose of carbamazepine meant that differences due to rate of rise of drug concentration were confounded with differences due to peak height.     

Pharmacokinetics of aripiprazole and concomitant carbamazepine

The objective of this study was to assess the pharmacokinetics of aripiprazole when coadministered with carbamazepine using an open-label sequential treatment design in patients with schizophrenia or schizoaffective disorder. Nine male patients were enrolled and received aripiprazole monotherapy (30 mg once daily) for 14 days, after which aripiprazole steady-state pharmacokinetics were assessed. Subjects were then administered carbamazepine together with aripiprazole for 4 to 6 weeks. The dose of carbamazepine was titrated to produce a trough serum concentration within the range of 8 to 12 mg/L. Aripiprazole pharmacokinetics were then assessed in the presence of carbamazepine. Six patients completed the study as designed. Coadministration with carbamazepine decreased the values of mean peak plasma concentration and area under the plasma concentration-time curve of aripiprazole by 66% and 71%, respectively (P = 0.001 and 0.002, respectively). Similarly, coadministration with carbamazepine decreased the values of mean peak plasma concentration and area under the plasma concentration-time curve over the 24-hour dosing interval of the major active metabolite of aripiprazole, dehydroaripiprazole, by 68% and 69%, respectively (P < 0.001). Both aripiprazole and dehydroaripiprazole are substrates for the cytochrome P-450 3A4 enzyme which is known to be induced by carbamazepine dosed to steady state. Thus, therapeutic doses of carbamazepine had significant effects on the pharmacokinetics of aripiprazole in patients with schizophrenia or schizoaffective disorder. When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled (to 20-30 mg/d). Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from combination therapy, aripiprazole dose should then be reduced.