三种中药制剂对卡马西平在小鼠体内药动学的影响

Effects of three Chinese medicines to the pharmacokinetics of carbamazepine in mice

目的:研究川芎嗪注射液、松龄血脉康胶囊和血脉通胶囊对小鼠体内卡马西平的药动学过程影响。方法:将昆明种雄性小鼠分为5组,分别灌胃给予卡马西平(120mg/kg)、卡马西平(120mg/kg)+盐酸川芎嗪注射液(40mg/kg)、卡马西平(120mg/kg)+松龄血脉康胶囊(900mg/kg)、卡马西平(120mg/kg)+血脉通胶囊(500mg/kg)、卡马西平(120mg/kg)+维拉帕米(30mg/kg),在不同时间点采集小鼠血样和脑组织,经处理后进行HPLC分析卡马西平血药浓度和脑组织浓度,绘制药-时曲线图,采用DAS2.0统计学软件计算主要的药动学数据。结果:与小鼠单一灌胃给予卡马西平的药动学参数相比,联合给予川芎嗪后,卡马西平在小鼠体内的药代动力学参数无明显改变;联合给予松龄血脉康胶囊后,小鼠血浆药动学参数Cmax增加了25.9%(P<0.05),其与参数无明显改变,但是小鼠脑组织药动学参数发生显著变化;联合给予血脉通胶囊和维拉帕米后,卡马西平除Tmax没有发生明显变化以外,其余药动学参数均发生显著变化。结论:血脉通胶囊(500mg/kg)可以显著影响卡马西平在小鼠体内的药动学过程,松龄血脉康胶囊(900mg/kg)则可以促进卡马西平在小鼠脑组织的分布,建议二者与卡马西平联用时加强临床观察,必要时监测卡马西平血药浓度或降低卡马西平的用量。

Objective： To investigate the effects of the three Chinese medicine on the pharmacokinetics of carbaraazepine in mice. Methods： Kunming mice were divided into five groups. The mice were received carbamazepine（120mg/kg） orally alone and combined with Ligustrazine Hydrochloride Injection （40mg/kg）, Songlingxuemaikang capsules （ 900mg/kg）, Xuemaitong capsules （500mg/kg） and verapamil （ 30mg/ kg）, respectively. Blood and brain tissue samples were collected at different time. After the samples were pretreated, they were detected by HPLC, and the concentration -time curves were obtained. The pharmacokinetie parameters were calculated using DAS 2.0. Results： Ligustrazine Hydrochloride Injection could not change the pharmaeokinetic parameters of carbamazepine significantly. And Songlingxuemaikang capsules increased the Cmax by 25.9% （P 〈0.05） in mice plasma, and no obvious changes in other parameters were bvserved. However, there had been significant changes in the brain pharmacokinetic parameters. More over, verapamil and Xuemaikang capsules could change all the pharmacokinetic parameters but Tmax. Condusion： Xuemaitong capsules （500mg/kg） could change the pharmacokinetie parameters of earbamazepine in mice, Songlingxuemaikang capsules（900mg/kg） could increase the cerebral distribution of carbamazepine in mice. Therefore, it is advisable to enhance clinical observation.