克班宁贴剂在大鼠体内的药动学与药效学评价  

Pharmacokinetic and Pharmacodynamic Evaluation of Crebanine Patch in Rats

作　　者：崔利利 李婧瑜 徐鹤 杨子贤 马云淑 CUI Li-li;LI Jing-yu;XU He;YANG Zi-xian;MA Yun-shu(College of Chinese Material Medica,Yunnan University of Chinese Medicine,Kunming 650500,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Yunnan Center for Disease Control and Prevention,Kunming 650000,China;Yunnan Key Laboratory of Dai and Yi Medicine,Kunming 650500,China;Yunnan Key Laboratory of Southern Medicinal Utilization,Kunming 650500,China)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]南京中医药大学药学院,江苏南京210023 [3]云南省疾病预防控制中心,云南昆明650000 [4]云南省傣彝学重点实验室,云南昆明650500 [5]云南省南药可持续利用重点实验室,云南昆明650500

出　　处：《南京中医药大学学报》2022年第11期1062-1068,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82060723,82174065)。

摘　　要：目的比较克班宁经皮和灌胃2种给药途径在大鼠体内的药动学差异性,评价克班宁贴剂经皮给药抗大鼠心律失常的效果,以及克班宁对钙离子通道的作用机制。方法采用HPLC法测定大鼠血浆中克班宁的浓度;采用氯化钡(BaCl 2)致大鼠心律失常的模型观察克班宁经皮给药的抗心律失常效果,采用Whole Cell记录检测克班宁对钙通道电流的影响。结果克班宁贴剂经皮给药(400 mg·kg^(-1))的主要药动学参数为:AUC 0-∞=(204.500±170.496)mg·h·L^(-1);T_(max)=(10.333±0.745)h;C_(max)=(1.968±0.147)mg·L^(-1)(n=6)。克班宁溶液灌胃给药(40 mg·kg^(-1))的主要药动学参数为:AUC 0-∞=(26.980±6.672)mg·h·L^(-1);T_(max)=(0.086±0.024)h;C_(max)=(8.991±2.343)mg·L^(-1)(n=6)。与阴性组比较,79、158、316 mg·kg^(-1)三个剂量克班宁贴剂组大鼠经皮给药后,恢复窦性心律所需的时间均显著缩短(P<0.01),恢复窦性心律的鼠数均明显增多(P<0.01);给药后≤20 min能够恢复窦性心律的鼠数均明显增多(P<0.001);恢复窦性心律后维持时间>20 min的鼠数显著增多(P<0.01)。克班宁对T型钙通道和L型钙通道均有较明显的抑制作用。结论克班宁贴剂给药在大鼠体内消除慢,具有缓释作用;克班宁灌胃给药在大鼠体内血药浓度变化符合一室模型,在体内消除快。克班宁贴剂,可通过抑制钙离子通道发挥对BaCl 2致大鼠心律失常的明显抑制作用,显著延长作用时间,达到减毒增效的目的。OBJECTIVE To compare the pharmacokinetic differences between the percutaneous and intragastric administration of Crebanine in rats.To evaluate the effect of Crebanine patch on anti-arrhythmia in rats and the mechanism of Crebanine on calcium channel.METHODS The plasma concentration of Crebanine in rats was determined by HPLC.The anti-arrhythmic effect of Crebanine transdermal administration was observed in the model of barium chloride induced arrhythmia in rats,and Whole Cell recording was used to detect the effect of Crebanine on calcium channel current.RESULTS The main pharmacokinetic parameters of Crebanine patch for transdermal administration(400 mg·kg^(-1))were as follows:AUC 0-∞=(204.500±170.496)mg·h·L^(-1);T_(max)=(10.333±0.745)h;C_(max)=(1.968±0.147)mg·L^(-1)(n=6).The main pharmacokinetic parameters of Crebanine solution for intragastric administration(40 mg·kg^(-1))were as follows:AUC 0-∞=(26.980±6.672)mg·h·L^(-1);T_(max)=(0.086±0.024)h;C_(max)=(8.991±2.343)mg·L^(-1)(n=6).Compared with the negative group,the time required for recovery of sinus rhythm was significantly shortened(P<0.01),and the number of rats recovering sinus rhythm significantly increased(P<0.01)after transdermal administration of the patches in 79,158,316 mg·kg^(-1) groups.The number of rats that could recover sinus rhythm within 20 min after administration increased significantly(P<0.001).The number of rats that maintained sinus rhythm for more than 20 min after the restoration increased significantly(P<0.01).Both T-type and L-type calcium channels were inhibited by Crebanine.CONCLUSION The administration of Crebanine patch has slow elimination and sustained release effect The change of plasma concentration of Crebanine by intragastric administration was consistent with the one-compartment model and eliminated quickly in vivo.Crebanine patch,can significantly inhibit barium chloride induced arrhythmia in rats by inhibiting calcium channels,and significantly prolong the action time,so as to achieve the purpose of redu

关 键 词：克班宁 贴剂 灌胃 药动学 抗心律失常 钙通道 

分 类 号：R285.5[医药卫生—中药学]