CN: 32-1845/R
ISSN: 2095-6975
引用本文:
0
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]. 中国天然药物英文, 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
摘要:
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).
关键词:    Hydrolysates of ginkgolides    LC-MS/MS    Pharmacokinetics    Ginkgo diterpene lactones    Beagle dog   
收稿日期: 2016-11-28
XIAO Wei,E-mail:xw_kanion@163.com;WANG Guang-Ji,E-mail:guangjiwang@hotmail.com
相关功能
PDF(682 KB) Free
打印本文
把本文推荐给朋友
作者相关文章
WANG Shu-Yao 在本刊中的所有文章
A Ji-Ye 在本刊中的所有文章
FEI Fei 在本刊中的所有文章
GENG Jian-Liang 在本刊中的所有文章
PENG Ying 在本刊中的所有文章
OUYANG Bing-Chen 在本刊中的所有文章
WANG Pei 在本刊中的所有文章
JIN Xiao-Liang 在本刊中的所有文章
ZHAO Yu-Qing 在本刊中的所有文章
WANG Jian-Kun 在本刊中的所有文章
GENG Ting 在本刊中的所有文章
LI Yan-Jing 在本刊中的所有文章
HUANG Wen-Zhe 在本刊中的所有文章
WANG Zhen-Zhong 在本刊中的所有文章
XIAO Wei 在本刊中的所有文章
WANG Guang-Ji 在本刊中的所有文章
参考文献:
[1] Saleem S, Zhuang H, Biswal S, et al. Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury[J]. Stroke, 2008, 39(12):3389-3396.
[2] Wang DL, Peng DY, Liu XD, et al. Pharmacokinetics, tissue distribution, excretion, and metabolism of a new cardioprotective agent 10-O-dimethylaminoethylginkgolide B in rats[J]. J Asian Nat Prod Res, 2012, 14(1):27-38.
[3] Mohanta TK, Tamboli Y, Zubaidha PK. Phytochemical and medicinal importance of Ginkgo biloba L.[J]. Nat Prod Res, 2014, 28(10):746-752.
[4] Suzuki E, Sato M, Takezawa R, et al. The facilitative effects of bilobalide, a unique constituent of Ginkgo biloba, on synaptic transmission and plasticity in hippocampal subfields[J]. J Physiol Sci, 2011, 61(5):421-427.
[5] Wu X, Su J, Chen L, et al. Ginkgolide B protects neurons from ischemic injury by inhibiting the expression of RTP801[J]. Cell Mol Neurobiol, 2015, 35(7):943-952.
[6] Muller WE, Heiser J, Leuner K. Effects of the standardized Ginkgo biloba extract EGb 761(R) on neuroplasticity[J]. Int Psychogeriatr, 2012, 24(Suppl 1):S21-24.
[7] Dodge HH, Zitzelberger T, Oken BS, et al. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline[J]. Neurology, 2008, 70(19 Pt 2):1809-1817.
[8] Mdzinarishvili A, Kiewert C, Kumar V, et al. Bilobalide prevents ischemia-induced edema formation in vitro and in vivo[J]. Neuroscience, 2007, 144(1):217-222.
[9] Priyanka A, Nisha VM, Anusree SS, et al. Bilobalide attenuates hypoxia induced oxidative stress, inflammation, and mitochondrial dysfunctions in 3T3-L1 adipocytes via its antioxidant potential[J]. Free Radic Res, 2014, 48(10):1206-1217.
[10] Ma W, Hu J, Cheng Y, et al. Ginkgolide B protects against cisplatin-induced ototoxicity:enhancement of Akt-Nrf2-HO-1 signaling and reduction of NADPH oxidase[J]. Cancer Chemother Pharmacol, 2015, 75(5):949-959.
[11] Wang X, Jiang CM, Wan HY, et al. Neuroprotection against permanent focal cerebral ischemia by ginkgolides A and B is associated with obstruction of the mitochondrial apoptotic pathway via inhibition of c-Jun N-terminal kinase in rats[J]. J Neurosci Res, 2014, 92(2):232-242.
[12] Wang W, Kang Q, Liu N, et al. Enhanced dissolution rate and oral bioavailability of Ginkgo biloba extract by preparing solid dispersion via hot-melt extrusion[J]. Fitoterapia, 2015, 102:189-197.
[13] Zheng B, Teng L, Xing G, et al. Proliposomes containing a bile salt for oral delivery of Ginkgo biloba extract:Formulation optimization, characterization, oral bioavailability and tissue distribution in rats[J]. Eur J Pharm Sci, 2015, 77:254-264.
[14] Huang P, Zhang L, Chai C, et al. Effects of food and gender on the pharmacokinetics of ginkgolides A, B, C and bilobalide in rats after oral dosing with ginkgo terpene lactones extract[J]. J Pharm Biomed Anal, 2014, 100:138-144.
[15] Wang DL, Peng DY, Tao XH, et al. The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma[J]. J Asian Nat Prod Res, 2013, 15(4):337-343.
[16] Wang J, Ouyang J, Liu Y, et al. Development of a sensitive LC-MS/MS method for the determination of bilobalide in rat plasma with special consideration of ex vivo bilobalide stability:application to a preclinical pharmacokinetic study[J]. J Pharm Biomed Anal, 2014, 95:238-244.
[17] Yuan C, Pan J, Hu X. Determination of the derivative from ginkgolide B[J]. Nat Prod Res, 2008, 22(15):1333-1338.
[18].Li XJ, Yang K, Du G, et al. Understanding the regioselective hydrolysis of ginkgolide B under physiological environment based on generation, detection, identification, and semi-quantification of the hydrolyzed products[J]. Anal Bioanal Chem, 2015, 407(26):7945-7956.
[19] Zhou XW, Ma Z, Geng T, et al. Evaluation of in vitro inhibition and induction of cytochrome P450 activities by hydrolyzed ginkgolides[J]. J Ethnopharmacol, 2014, 158(Pt A):132-139.
[20] Liu XG, Qi LW, Fan ZY, et al. Accurate analysis of ginkgolides and their hydrolyzed metabolites by analytical supercritical fluid chromatography hybrid tandem mass spectrometry[J]. J Chromatogr A, 2015, 1388:251-258.
[21] Li XJ, Wang YQ, Yang J, et al. Semi-quantitative determination of monocarboxylate forms of ginkgolide B in plasma by UPLC-MS[J]. Anal Bioanal Chem, 2015, 407(14):4121-4129.
[22] Song H, Bu F, Wei C, et al. Pharmacokinetics of ginkgolide B injection in beagle dogs[J]. Arzneimittelforschung, 2012, 62(12):595-598.
[23] Hua L, Guangji W, Hao L, et al. Sensitive and selective liquid chromatography-electrospray ionization mass spectrometry analysis of ginkgolide B in dog plasma[J]. J Pharm Biomed Anal, 2006, 40(1):88-94.
[24] Services USDoHaH. Analytical procedures and methods validation for drugs and biologics[R]. 2015.
[25] Wang S, Ouyang B, Aa J, et al. Pharmacokinetics and tissue distribution of ginkgolide A, ginkgolide B, and ginkgolide K after intravenous infusion of ginkgo diterpene lactones in a rat model[J]. J Pharm Biomed Anal, 2016, 126:109-116.

相关文章:
1.DOU Li-Li, DUAN Li, GUO Long, LIU Le-Le, ZHANG Yu-Dong, LI Ping, LIU E-Hu.An UHPLC-MS/MS method for simultaneous determination of quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, isorhamnetin 3-O-rutinoside, bilobalide and ligustrazine in rat plasma, and its application to pharmacokinetic study of Xingxiong injection[J]. 中国天然药物, 2017,15(9): 710-720
2.GU Pan, LIU Rui-Juan, CHENG Min-Lu, WU Yao, ZHENG Lu, LIU Yu-Jie, MA Peng-Cheng, DING Li.Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets[J]. 中国天然药物, 2016,14(4): 313-320
3.CHEN Qian-Qian, GUO Jian-Ru, FENG Suo-Ming, WANG Cai-Yun, ZHANG Wei.Quantitation of ligupurpurosides B and C in rat plasma using HPLC-MS/MS[J]. 中国天然药物, 2016,14(6): 473-480
4.YU Jun-Xian, Sukesh Voruganti, LI Dan-Dan, Jiang-Jiang Qin, Subhasree Nag, Su Xu, Sadanandan E. Velu, Wei Wang, Ruiwen ZHANG.Development and validation of an HPLC-MS/MS analytical method for quantitative analysis of TCBA-TPQ, a novel anticancer makaluvamine analog, and application in a pharmacokinetic study in rats[J]. 中国天然药物, 2015,13(7): 554-560
5.ZHANG Wei, HUO Shi-Xia, WEN Yan-Li, XING Han, ZHANG Qing, LI Ning, ZHAO Di, SUN Xiao-Lin, XU Jie, YAN Ming, CHEN Xi-Jing.Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs[J]. 中国天然药物, 2015,13(8): 634-640
6.ZHAN Qin, ZHANG Feng, GAO Shou-Hong, CAI Fei, JIANG Bo, SUN Lian-Na, CHEN Wan-Sheng.An HPLC-MS/MS method for the quantitative determination of platycodin D in rat plasma and its application to the pharmacokinetics of Platycodi Radix extract[J]. 中国天然药物, 2014,12(2): 154-160