Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs

作     者：WANG Shu-Yao A Ji-Ye FEI Fei GENG Jian-Liang PENG Ying OUYANG Bing-Chen WANG Pei JIN Xiao-Liang ZHAO Yu-Qing WANG Jian-Kun GENG Ting LI Yan-Jing HUA NG Wen-Zhe WANG Zhen-Zhong XIAO Wei WANG Guang-Ji 

作者机构：School of Chinese Pharmacy Beijing University of Chinese Medicine Beijing 100102 China Jiangsu Kanion Modern Chinese Medicine Institute Nanjing 210017 China State Key Labonatory of Pharmaceutical New-Techfor Chinese Medicine Jiangsu Kanion Pharmaceutical Co. Ltd. Lianyungang222001 China Key Lab of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009 China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2017年第15卷第10期

页      面：775-784页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 100706[医学-药理学] 1002[医学-临床医学] 0703[理学-化学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：financially supported by the National Key Special Project of Science and Technology for Innovation Drugs of China(Nos.2013zx09402203 and 2013zx09402202) the Natural Science Foundation of Jiangsu Province,China(No.BK20130403) the National Natural Science Foundation of China(No.81503342) the Project for Jiangsu Province Key Lab of Drug Metabolism and Pharmacokinetics(No.BM2012012) 

主　　题：Hydrolysates of ginkgolides LC-MS/MS Pharmacokinetics Ginkgo diterpene lactones Beagle dog 

摘      要：Ginkgo diterpene lactones meglumine injection(GDLI)is a commercially available product used for ***,the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI,i.e.,ginkgolide A(GA),ginkgolide B(GB),and ginkgolide K(GK),have never been fully evaluated in beagle *** this work,a simple,sensitive,and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry(UFLC-MS/MS)was developed,and the prototypes and total amounts of GA,GB,and GK were determined in beagle dog *** plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone *** the first time,the pharmacokinetics of GA,GB,and GK were fully assessed in three forms,i.e.,the prototypes,the hydrolyzed carboxylic forms,and the total amounts,after intravenous administration of GDLI in beagle *** was shown that ginkgolides primarily existed in the hydrolyzed form in plasma,and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic *** of the three forms of the three ginkgolides showed linear exposure of AUC to the ***,GB,and GK showed a constant half-life approximately 2.7,3.4,and 1.2 h,respectively,which were consistent for the forms at three dose levels(0.3,1.0,and 3.0 mg·kg^(-1))and after a consecutive injection of GDLI for 7 days(1.0 mg·kg^(-1)).