牛蒡子苷元大鼠皮下注射给药后的血浆动力学及组织分布研究  

Plasma Kinetics and Tissue Distribution of Arctigenin in Rats after Subcutaneous Injection

作　　者：韩舒[1,2] 谷元[2] 杨元辉[2] 商庆节 姚景春 刘万卉[1] 司端运[2] HAN Shu GU Yuan YANG Yuan-hui SHANG Qing-jie YAO Jing-chun LIU Wan-hui SI Duan-yun(School of Pharmacy, Yantai University, Yantai 264005, China State Key Laboratory of Drug Delivery Technology and Pharma- cokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China State Key Laboratory of Generic Manufacture Tech- nology of Chinese Traditional Medicine, Linyi 276000, China)

机构地区：[1]烟台大学药学院,山东烟台264005 [2]天津药物研究院有限公司释药技术与药代动力学国家重点实验室,天津300193 [3]中药制药共性技术国家重点实验室,山东临沂276000

出　　处：《烟台大学学报（自然科学与工程版）》2017年第2期131-137,共7页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：国家自然科学基金资助项目(81503154);山东省自主创新及成果转化专项计划项目(2015ZDJQ05004)

摘　　要：本研究采用大鼠皮下注射牛蒡子苷元注射液,并对给药后的系统暴露动力学特征进行评价.大鼠皮下注射0.1、0.3、1.0 mg/kg牛蒡子苷元注射液,应用LC-MS/MS法测定牛蒡子苷元不同时间点的血浆/组织浓度,并计算药代动力学参数.大鼠皮下注射3种剂量牛蒡子苷元注射液后,T_(max)均为0.3 h左右,C_(max)分别为17.6±4.74、61.8±8.05、285±77.0 ng/m L,AUC_(0-t)分别为22.8±5.77、83.5±15.3、412±117 h·ng/mL,t1/2为0.781~1.08 h,V_d为3.84~5.59 L/kg,绝对生物利用度为103%.牛蒡子苷元在大鼠组织中分布迅速、广泛,其中肠、心、肝、胰、肾等组织中药物含量较高(>血浆暴露量)且无明显蓄积现象.牛蒡子苷元注射液皮下注射给药后,在大鼠体内吸收迅速,C_(max)及AUC_(0-t)与剂量呈正相关、分布广泛、清除较快,可有效提高其在大鼠循环系统及组织中的暴露水平,并呈良好的动力学特征.The plasma kinetics and tissue distribution of arctigenin after subcutaneous injection in Wistar rats are investigated. Wistar rats are injected subcutaneously with arctigeninare of 0.1,0.3 and 1.0 mg/kg, blood and tissue samples are collected at different time points after injection, and concentrations of arctigenin in the samples are determined by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. After subcutaneous injection arctigenin 0.1,0.3 and 1.0 mg/kg, Tin.x of the 3 groups is 0.3 h, AUC is 22.8 ±5.77, 83.5 ± 15.3 and 412 ± 117 h · ng/mL respectively, Cmax is 17.6 ± 4.74, 61.8 ± 8.05 and 285 ± 77.0 ng/mL respectively, t1/2 is 0.781 - 1.08 h, Vd is 3.84-~ 5.59 L/kg, and the calculated absolute bioavailability is 103%. Aretigenin is quickly and widely distributed in Wistar rats organs, and mainly distributes in intestine, heart, liver, pancreas and kidney without apparent accumulating effect. Arctigenin is absorbed and eliminated quickly in Wistar rats after subcutaneous injection, the distribution is wide, and Cmox and AUC0-t are in a linear proportion to arctigenin dose. It is concluded that subcutaneous injection can effectively improve the level of systemic and tissular exposure in rats, and shows good kinetics.

关 键 词：牛蒡子苷元 皮下注射 血浆动力学 组织分布 液相色谱串联质谱联用 

分 类 号：R969.1[医药卫生—药理学]