资源描述：
《Influence of Hepatic Impairment》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、ClinicalTherapeutics/Volume33,Number11,2011InfluenceofHepaticImpairmentonthePharmacokineticsandSafetyProfileofDapagliflozin:AnOpen-Label,Parallel-Group,Single-DoseStudy121,SreeneeranjKasichayanula,PhD;XiaoniLiu,PhD;WeijiangZhang,PhD*;111MarcPfister,MD,FCP;FrankP.LaCreta,PhD;andDavidW.Bou
2、lton,PhD1DiscoveryMedicineandClinicalPharmacology,Bristol-MyersSquibbCo,Princeton,NewJersey;and2GlobalBiometricSciences,Bristol-MyersSquibbCo,Princeton,NewJerseyABSTRACT3%,36%,and67%highercomparedwithhealthyBackground:Dapaglißozin,aselectiveinhibitorofsubjects,respectively.Dapaglißoz
3、in3-O-glucuroniderenalsodiumglucoseco-transporter2,isunderdevel-meanCmaxvalueswere4%and58%higherand14%opmentforthetreatmentoftype2diabetesmellitus.lowerinthosewithmild,moderate,orsevereHIcom-Dapaglißozineliminationisprimarilyviaglucuroni-paredwithhealthysubjects,respectively,andmeand
4、ationtoaninactivemetabolite,dapaglißozin3-O-dapaglißozin3-O-glucuronideAUC0Ðvalueswereglucuronide.Pharmacokineticstudiesarerecom-6%,100%,and30%highercomparedwithhealthymendedinsubjectswithimpairedhepaticfunctionifsubjects,respectively.Thesevalueswerehighlydepen-hepaticmetabolismacco
5、untsforasubstantialpor-dentonthecalculatedcreatinineclearanceofeachtionoftheabsorbeddrug.group.Alladverseeventsweremildormoderate,withObjective:Thepurposeofourstudywastocomparenoimbalanceinfrequencybetweengroups.thepharmacokineticsofdapaglißozininpatientswithConclusions:Comparedwithh
6、ealthysubjects,sys-mild,moderate,orseverehepaticimpairment(HI)temicexposuretodapaglißozininsubjectswithHIwaswithhealthysubjects.correlatedwiththedegreeofHI.Single10-mgdosesofMethods:Thiswasanopen-label,parallel-groupdapaglißozinweregenerallywelltoleratedbypartici-studyinmaleorfemalep
7、atientswithmild,moderate,pantsinthisstudy.DuetothehigherdapaglißozinorsevereHI(6pergroupaccordingtoChild-PughexposuresinpatientswithsevereHI,thebeneÞt:riskclassiÞcation)andin6healthycontrolsubjects.Theratioshouldbeindividuallyassessedbecausethelong-controlsubjectswerematchedtothecomb
8、inedHItermsa
