CN: 32-1845/R
ISSN: 2095-6975
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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, HUANG Wen-Zhe, WANG Zhen-Zhong, XIAO Wei, WANG Guang-Ji. 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[J]. Chinese Journal of Natural Medicines, 2017, 15(10): 775-784

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

WANG Shu-Yao1,2,3, A Ji-Ye4, FEI Fei4, GENG Jian-Liang4, PENG Ying4, OUYANG Bing-Chen4, WANG Pei4, JIN Xiao-Liang4, ZHAO Yu-Qing4, WANG Jian-Kun4, GENG Ting2,3, LI Yan-Jing2,3, HUANG Wen-Zhe2,3, WANG Zhen-Zhong2,3, XIAO Wei1,2,3, WANG Guang-Ji4
1 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China;
2 Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China;
3 State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China;
4 Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Abstract:
Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, 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 dogs. In 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. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For 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 dogs. It 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 ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, 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).
Key words:    Hydrolysates of ginkgolides    LC-MS/MS    Pharmacokinetics    Ginkgo diterpene lactones    Beagle dog   
Received: 2016-11-28   Revised:
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Articles by WANG Shu-Yao
Articles by A Ji-Ye
Articles by FEI Fei
Articles by GENG Jian-Liang
Articles by PENG Ying
Articles by OUYANG Bing-Chen
Articles by WANG Pei
Articles by JIN Xiao-Liang
Articles by ZHAO Yu-Qing
Articles by WANG Jian-Kun
Articles by GENG Ting
Articles by LI Yan-Jing
Articles by HUANG Wen-Zhe
Articles by WANG Zhen-Zhong
Articles by XIAO Wei
Articles by WANG Guang-Ji
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