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1、510CurrentDrugMetabolism,2012,13,510-523MetaboliteProfilingandPharmacokineticsofHerbalCompoundsFollowingOralAdministrationofaCardiovascularMulti-herbMedicine(QishenYiqiPills)inRat§§YufengZhang,PeiyingShi,HongYao,QingShaoandXiaohuiFan*DepartmentofChineseMedicineScience&Eng
2、ineering,CollegeofPharmaceuticalSciences,ZhejiangUniversity,Hangzhou310058,P.R.ChinaAbstract:Qishenyiqipills(QYpills)areatypeofstandardizedcardiovascularherbalmedicine,whichcontainfourcomponentherbs,i.e.,Astragalusmembranaceus(Huangqi),Salviamiltiorrhiza(Danshen),Panaxnoto
3、ginseng(Sanqi),andDalbergiaodorifera(Ji-angxiang).AfteroraladministrationofQYpills,theinvivoexposuretypesofeachcomponentherbinratswerefirstuncoveredandiden-tifiedaccordingtoatarget-directedstrategybasedonhyphenatedchromatographytechniques.Thedominatedmetabolitesinurine,blo
4、odandbilewereoriginatedfromflavonoidsofHuangqiandmonomerphenolicacidsofDanshen;nometabolitesbutparentdrugsofSanqiginsenosides,namelyginsenosidesRb1,Rd,ReandRg1,notoginsenosideR1andgypenosideXVII,weredetectedinraturineandblood,andthe20(S)-protopanaxatrioltypeginsenosides(NR
5、1,GRe,GRg1)couldalsobeexcretedtobile;thehighliposolubilityofvolatileoilsfromJiangxiangrestrictedthemtosmallintestine,liverandadiposetissues.Theidentificationofmetabolitesinbio-sampleswasachievedbyexactmassmeasurementanddetailedfragmentationpathwayanalyses.Inspecificconditi
6、ons,notonlythetypesofphaseIImetabolismbutalsotheirconjugationpositionscouldbedeterminedbyourestablishedcleavagepathways,whichleadtodiscriminatethephaseIImetabolitesofprotocatechualdehydeforthefirsttime.Basedonthemetabolitestudyinrats,the4maincompounds(tanshi-nol,astragalos
7、ideIV,GRb1andGRg1)inQYpillswereselectedaspharmacokineticmarkers.ThePKresultsshowedthattheirmaximalconcentrationsinbloodwereobtainedwithinonehour,muchshorterthanthereportedvaluesinsingleherbs.Theratexposurewasproximatelylinearunderthestudieddosagesfrom1to6g/kg.Keywords:Chin
8、eseherbalmedicine,metabolism,pharmacokinetics,qishenyiqipills.INTRODUCTIONmulti-herbprepa
