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1、IntroductiontoDrugMetabolismTHIRDEDITIONG.GordonGibsonPhDProfessorofMolecularToxicologySchoolofBiomedicalandLifeSciencesUniversityofSurrey,EnglandPaulSkettFil.Dr.SeniorLecturerinPharmacologyUniversityofGlasgow,ScotlandText#G.GordonGibsonandPaulSkett1986,1994,2
2、001Originalillustrations#NelsonThornesLtd1986,1994,2001TherightofG.GordonGibsonandPaulSketttobebeidenti?edasauthorsofthisworkhasbeenassertedbytheminaccordancewiththeCopyright,DesignsandPatentsAct1988.Allrightsreserved.Nopartofthispublicationmaybereproducedortr
3、ansmittedinanyformorbyanymeans,electronicormechanical,includingphotocopying,recordingoranyinformationstorageandretrievalsystem,withoutpermissioninwritingfromthepublisherorunderlicencefromtheCopyrightLicensingAgencyLimitedof90TottenhamCourtRoad,LondonW1T4LP.Fir
4、steditionpublishedin1986by:Chapman&HallSecondeditionpublishedin1994Thirdeditionpublishedin2001by:NelsonThornesPublishersDeltaPlace27BathRoadCheltenhamGL537THUnitedKingdom0102030405/10987654321AcataloguerecordforthisbookisavailablefromtheBritishLibraryISBN07487
5、60113ThecovershowsapartialviewofthedockingofcarbemazepinewiththeactivesiteofCYP3A4.CourtesyofDrDaveLewis,SchoolofBiomedicalandLifeSciences,UniversityofSurrey,England.Everyefforthasbeenmadetocontactcopyrightholdersofanymaterialreproducedwithinthetextandtheautho
6、rsandpublishersapologiseifanyhavebeenoverlookedTypesetbyAarontypeLimited,Easton,BristolPrintedandboundinSpainbyGraphyCemsCONTENTS1PATHWAYSOFDRUGMETABOLISM11.1Introduction11.2Phase1metabolism21.2.1OxidationsinvolvingcytochromeP450(themicrosomalmixed-functionoxi
7、dase)31.2.2OxidationsnotcatalysedbycytochromeP45081.2.3Reductivemetabolism101.2.4Hydrolysis111.2.5Hydration121.2.6Otherphase1reactions131.2.7Summaryofphase1metabolism131.3Phase2metabolism141.3.1Conjugationwithsugars141.3.2Sulfation171.3.3Methylation181.3.4Acet
8、ylation201.3.5Aminoacidconjugation211.3.6Glutathioneconjugation211.3.7Fattyacidconjugation241.3.8Summaryofphase2metabolism241.3.9Stereoselectivereactions241.4Summaryofdrug-metaboli
