Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs

Molecules

Jie Zhao¹  Ting Geng¹  Qi Wang²  Haihong Si¹  Xiaoping Sun¹  Qingming Guo¹  Yanjing Li¹  Wenzhe Huang¹  Gang Ding¹  Wei Xiao¹ 

[1] State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222000, China;Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China;

关键词: ginkgolide B;    hot-melt extrusion;    liquid layer;    beagle dog plasma;    pharmacokinetics;    LC-MS/MS;   

DOI  :  10.3390/molecules201119678

来源: mdpi

【 摘 要 】

Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C₁₈ column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The C_max values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.

【 授权许可】

CC BY   
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