A sensitive LC-MS/MS method to determine ginkgolide B in human plasma and urine: application in a pharmacokinetics and excretion study of healthy Chinese subjects. (3rd March 2020)

• Record Type: Journal Article
• Authors: Shen, Chenlin; Jin, Xiaoqin; Wu, Maomao; Huang, Xiaohui; Li, Jun; Huang, Hong; Li, Feilong; Liu, Jiatao; Rong, Genxiang; Song, Shuai
• Is Part Of: Xenobiotica. Volume 50:Number 3(2020:Mar.)
• Page Start: 323
• Page End: 331
• Publication Date: 2020-03-03
• Subjects: Ginkgolide B -- LC-MS/MS -- human plasma and urine -- pharmacokinetics -- excretion; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2019.1612124
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. Ginkgolide B (GB), the most active of the ginkgolides, has been developed as a new drug for the treatment of vascular insufficiency; however, the pharmacokinetics of GB remain unclear. Here, we investigated the pharmacokinetics and urine excretion properties of GB in healthy Chinese subjects administered single- and multiple-dose injectable GB based on a new LC-MS/MS method. 2. GB pharmacokinetics were found to be dose-dependent from 20 to 60 mg. GB reached a steady state by day 6 with once-daily dosing at 40 mg. Systemic exposure to GB, as characterised by AUC 0–∞, indicated accumulation following repeated once-daily dosing for seven consecutive days. The mean urinary cumulative excretion rate of GB in response to 20, 40, and 60 mg GB was 41.9 ± 18.5%, 32.9 ± 12.2%, and 43.9 ± 8.5%, respectively. 3. Dose-proportional pharmacokinetics of GB were observed after intravenous administration in healthy subjects. A gradual reduction in the volume of distribution and slight change in mean resistance time led us to conjecture the limited accumulation of GB based on distribution equilibrium in vivo . 4. This comprehensive study of the clinical pharmacokinetics of GB will provide useful information for its application and further development.