摘要
目的:研究金匮肾气总苷中马钱苷的在体肠吸收机制和药代动力学规律。方法:采用大鼠在体肠循环灌流法,考察药物质量浓度、肠道的pH值、不同肠段及P-gp对总苷中马钱苷肠吸收的影响;给大鼠灌胃不同浓度的总苷,于不同时间点眼眶静脉丛采血,HPLC法测定马钱苷的质量浓度,通过3P97软件进行数据处理。结果:在0.01-0.11 mg·mL^(-1)范围内,总苷中马钱苷的吸收与浓度呈线性关系,不受肠道pH的影响,在十二指肠的吸收明显优于空肠及回肠,利福平和维拉帕米分别呈现出对马钱苷吸收的抑制和促进作用。各剂量组马钱苷的药动学行为呈线性关系,吸收、消除均较快,以一室开放模型在体内分布,与维拉帕米合用后,可显著促进马钱苷的吸收。结论:金匮肾气总苷中马钱苷的吸收呈一级动力学过程,推测为被动扩散,其吸收受到P-gp外排作用的影响,从药动学的角度得以验证。
This study aimed at studying the intestinal absorption mechanism and pharmacokinetics of Semen Strychni in total glycosides of Jinkuishenqi Pills.The effects of drug concentration,p H of intestinal tract,different intestinal segments and P-gp on the absorption of Semen Strychni in total glycosides were investigated by the intestinal circulation perfusion method.Following oral administration of total glycosides at different concentrations,the blood was collected at different time from rats’ orbital venous plexus.The concentration of Semen Strychni was measured by HPLC,and the 3 P97 software was used for data processing.The results showed that,the absorption and concentration of Semen Strychni in the total glycosides were linear in the range of 0.01-0.11 mg·mL-1,and were not affected by the intestinal PH.The absorption of the duodenum was obviously better than that of the jejunum and the ileum.Rifampin and vera pammy respaectively showed inhibitory and promoting effects on the absorption of Semen Strychni.The pharmacokinetic behavior of the Semen Strychni in each dose group was linear.The absorption and elimination were both fast,and distributed in vivo by one compartment open model.Vera pammy could significantly promote the absorption of Semen Strychni.The absorption of Semen Strychni in total glycosides of Jinkuishenqi Pills is a first-order kinetic process,which is presumed as passive diffusion.And its absorption is influenced by the P-gp efflux,which is verified from the perspective of pharmacokinetics.
作者
孙向明
宋辉
胡扬
丁晶鑫
李文兰
Sun Xiangming;Song Hui;Hu Yang;Ding Jingxin;Li Wenlan(School of Pharmacy,Harbin University of Commerce,Harbin,150076,China;Research Center of Life Sciences and Environmental Sciences,Harbin University of Commerce,Harbin,150076,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2018年第8期1422-1429,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
黑龙江省教育厅黑龙江省高校科技成果产业化前期研发培育项目(1254CGZH37):金匮肾气丸的中试研究,负责人:李文兰
黑龙江省教育局普通本科高等学校青年创新人才培养计划(UNPYSCT-2018135):基于协同效应的菟丝子拟雌激素作用等效成分群发现,负责人:孙向明.
关键词
金匮肾气总苷
马钱苷
肠吸收
药代动力学
Total glycosides of Jinkuishenqi Pills
Semen Strychni
intestinal absorption
pharmacokinetics
