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.
10.1016/S1875-5364(17)30109-7
- Author:
Shu-Yao WANG
1
,
2
,
3
;
Ji-Ye A
4
;
Fei FEI
4
;
Jian-Liang GENG
4
;
Ying PENG
4
;
Bing-Chen OUYANG
4
;
Pei WANG
4
;
Xiao-Liang JIN
4
;
Yu-Qing ZHAO
4
;
Jian-Kun WANG
4
;
Ting GENG
3
,
5
;
Yan-Jing LI
3
,
5
;
Wen-Zhe HUANG
3
,
5
;
Zhen-Zhong WANG
3
,
5
;
Wei XIAO
1
,
2
,
6
;
Guang-Ji WANG
7
Author Information
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.
5. Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China
6. State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China. Electronic address: xw_kanion@163.com.
7. Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: guangjiwang@hotmail.com.
- Publication Type:Journal Article
- Keywords:
Beagle dog;
Ginkgo diterpene lactones;
Hydrolysates of ginkgolides;
LC-MS/MS;
Pharmacokinetics
- MeSH:
Animals;
Dogs;
Ginkgo biloba;
chemistry;
Ginkgolides;
administration & dosage;
pharmacokinetics;
Lactones;
administration & dosage;
pharmacokinetics;
Plant Extracts;
administration & dosage;
pharmacokinetics;
Tandem Mass Spectrometry
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(10):775-784
- CountryChina
- Language:English
-
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) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg).
