酸浆苦味素B在大鼠体内的药代动力学参数及组织分布研究  

Study on Pharmacokinetics and Tissue Distribution of Physalin B in Rats

作　　者：王勇[1] 张炯怡 谢明军 宋晓宁 马莹[1] 张志勇[1] WANG Yong;ZHANG Jiong-yi;XIE Ming-jun;SONG Xiao-ning;MA Ying;ZHANG Zhi-yong(Guizhou Provincial Institute for Food and Drug Control,Guiyang,Guizhou,550004,China;Guizhou Institute of Food Inspection & Testing,Guiyang,Guizhou,550004,China;Guizhou Medical Products Administration,Guiyang,Guizhou,550004,China)

机构地区：[1]贵州省食品药品检验所,贵州贵阳550004 [2]贵州省食品检验检测院,贵州贵阳550004 [3]贵州省药品监督管理局,贵州贵阳550004

出　　处：《动物医学进展》2021年第12期72-80,共9页Progress In Veterinary Medicine

基　　金：贵州省科技厅科技支撑项目(黔科合[2016]支撑);贵州省科技厅科技支撑项目(黔科合SY字[2015]3032)。

摘　　要：建立大鼠血浆和组织中酸浆苦味素B的含量测定方法,研究酸浆苦味素B在大鼠体内的药代动力学过程及组织分布。以4.968、9.935、19.87 mg/kg 3个剂量酸浆苦味素B灌胃大鼠,采集血浆和组织样品,然后采用UPLC-MS/MS法测定大鼠血浆和组织中的酸浆苦味素B浓度,研究酸浆苦味素B药代动力学参数及组织分布情况。结果显示,在大鼠血浆和组织中,酸浆苦味素B在1.3 ng/mL~1300 ng/mL和1.3 ng/mL~6500 ng/mL范围内线性关系良好,日内、日间精密度均小于15%,提取回收率为94.17%~118.77%。酸浆苦味素B低、中、高3个剂量组在体内的主要药代动力学参数:达峰时间tmax均为0.667 h,达峰浓度Cmax分别为(169.0866.641)μg/L、(247.51323.434)μg/L和(619.56728.201)μg/L,半衰期t1/2z分别为(8.9752.966)h、(10.0223.196)h和(5.9122.271)h,药时曲线下面积AUC(0-t)分别为(748.73547.13)μg/L·h、(1189.897100.436)μg/L·h和(2963.312176.7)μg/L·h,说明酸浆苦味素B在体内吸收快,消除较慢,曲线下面积(AUC)与剂量之间呈线性关系。大鼠灌胃给药19.87 mg/kg后,20 min的组织分布顺序为胃>十二指肠>肺>卵巢>脂肪>肾>肝>小肠>直肠>大肠>脾>心>肌肉>脑;50 min的组织分布顺序为胃>十二指肠>小肠>肾>脂肪>卵巢>肝>脾>直肠>心>肺>大肠>肌肉>脑;180 min的组织分布顺序为十二指肠>胃>肝>小肠>脂肪>大肠>直肠>肺>心>卵巢>肌肉>肾>脾>脑。说明酸浆苦味素B在大鼠体内组织分布广泛,不同时间点药物浓度以胃中相对较高,推测其可能对胃有一定的靶向性。试验建立的UPLC-MS/MS检测方法操作简便、精密度高,适用于酸浆苦味素B在大鼠体内的药代动力学和组织分布研究,为酸浆苦味素B作用机制研究及药物开发提供一定的参考。The present study aimed to establish a method for the determination of physalin B in plasma and tissues of rats and to study the pharmacokinetics and tissue distribution of physalin B after oral administration in rats.After oral administration of physalin B at doses of 4.968 mg/kg,9.935 mg/kg and 19.87 mg/kg to rats,plasma and tissue samples were collected,and the concentrations of physalin B in rats plasma and tissues were measured by UPLC-MS/MS method to study plasma drug parameters and tissue distribution of physalin B.Physalin B showed a good linear relationship in the plasma and tissues of rats in the concentration range of 1.3 ng/mL-1300 ng/mL,1.3 ng/mL-6500 ng/mL.The intraday and interday precisions are less than 15%,and the accuracy is between 94.17%and 118.77%.The main pharmacokinetic parameters of physalin B at three dosage groups were as follows:tmax were all 0.667 h;Cmax were(169.0866.641)μg/L,(247.51323.434)μg/L and(619.56728.201)μg/L respectively;t1/2 were(8.9752.966)h,(10.0223.196)h and(5.9122.271)h respectively;AUC(0-t)were(748.73547.13)μg/L·h,(1189.897100.436)μg/L·h and(2963.312176.7)μg/L·h respectively.The results indicated that physalin B was absorbed rapidly and eliminated slowly after oral administration,and there was a linear relationship between AUC and the dose.After oral administration(19.87 mg/kg),the distribution of physalin B in 20 minutes was stomach>duodenum>lung>ovary>fat>kidney>liver>small intestine>rectum>large intestine>spleen>heart>muscle>brain;the distribution of physalin B in 50 minutes was stomach>duodenum>small intestine>kidney>fat>ovary>liver>spleen>rectum>heart>lung>large intestine>muscle>brain;the distribution of physalin B in 180 minutes was duodenum>stomach>liver>small intestine>fat>large intestine>rectum>lung>heart>ovary>muscle>kidney>spleen>brain.The results showed that physalin B was widely distributed in body tissues and stomach kept higher concentrations among various tissues at different time,so it can be speculated that physalin B may have certain target

关 键 词：酸浆苦味素B 药代动力学 组织分布 大鼠 

分 类 号：S859.7[农业科学—临床兽医学]