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 c...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)).展开更多
基金financially supported by the National Key Special Project of Science and Technology for Innovation Drugs of China(Nos.2013zx09402203 and 2013zx09402202)the Natural Science Foundation of Jiangsu Province,China(No.BK20130403)+1 种基金the National Natural Science Foundation of China(No.81503342)the Project for Jiangsu Province Key Lab of Drug Metabolism and Pharmacokinetics(No.BM2012012)
文摘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)).
