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

Ginkgoditerpenelactonesmeglumineinjection(GDLI)isacommerciallyavailableproductusedforneuroprotection.However,thepharmacokineticpropertiesoftheprototypesandhydrolyzedcarboxylicformsoftheprimarycomponentsinGDLI,i.e.,ginkgolideA(GA),ginkgolideB(GB),andginkgolideK(GK),haveneverbeenfullyevaluatedinbeagledogs.Inthiswork,asimple,sensitive,andreliablemethodbasedonultra-fastliquidchromatography-tandemmassspectrometry(UFLC-MS/MS)wasdeveloped,andtheprototypesandtotalamountsofGA,GB,andGKweredeterminedinbeagledogplasma.Theplasmaconcentrationsofthehydrolyzedcarboxylicformswerecalculatedbysubtractingtheprototypeconcentrationsfromthetotallactoneconcentrations.Forthefirsttime,thepharmacokineticsofGA,GB,andGKwerefullyassessedinthreeforms,i.e.,theprototypes,thehydrolyzedcarboxylicforms,andthetotalamounts,afterintravenousadministrationofGDLIinbeagledogs.Itwasshownthatginkgolidesprimarilyexistedinthehydrolyzedforminplasma,andtheratioofhydrolysatestoprototypeformsofGAandGBdecreasedgraduallytoahomeostaticratio.AllofthethreeformsofthethreeginkgolidesshowedlinearexposureofAUCtothedosages.GA,GB,andGKshowedaconstanthalf-lifeapproximately2.7,3.4,and1.2h,respectively,whichwereconsistentfortheformsatthreedoselevels(0.3,1.0,and3.0mg·kg~(-1))andafteraconsecutiveinjectionofGDLIfor7days(1.0mg·kg~(-1)).