西地那非治疗肺动脉高压的研究-吴文汇

2011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.15(200433),,55,,;,;;5R5432;R9A1672-3384(2011)-01-0005-07(pulmonaryarterialhypertension,PAH),(pulmonaryvesselresistance,PVR),[1],,,5[2](NIH)(primarypulmonaryhypertension,PPH)13568%,48%34%[3](idiopathicpulmonaryarterialhypertension,IPAH)(familialpulmonaryarterialhypertension,FPAH)123568%,569%,389%208%[4]5(phosphodiesterasetype5inhibitors,PDEI5)PAH,,[5-7],,[8],,1(nitricoxide,NO)(pulmonaryarterysmoothmusclecells,PASMCs)5(phosphodiesterasetype5,PDE5)[8]NOPASMCs,(cyclicWHO,WHO,,[1]ForgueST,PattersonBE,BeddingAW,eta.lTadalafilpharmacokineticsinhealthysubjects[J].BritishJournalofClinicalPharmacology.2005,61:280288.[2]TessierRB,AzdinelloM,FioriH,eta.lTadalafilimprovesoxygenationinamodelofnewbornpulmonaryhypertension[J].PediatrCritCareMed,2008,9:3302.[3]TsaiBM,TurrentineMW,SheridanBC,eta.lDifferentialeffectsofphosphodiesterase-5inhibitorsonhypoxicpulmonaryvasoconstrictionandpulmonaryarterycytokineexpression[J].AnnThoracSurg,2006,81:272278.[4]GalieN,BrundageBH,GhofraniHA,eta.lTadalafiltherapyforpulmonaryarterialhypertension[J].Circulation,2009,119:2894903.2011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.16guanosine3,'5-'monophosphate,cGMP),,,,,[9-10],NO,cGMP,3,(cyclicadenosinemonophosphate,cAMP),PDE5,cGMPcAMP,,[11]PDE5,NO/cGMP,,,,,(1)[9-12]15221健康志愿者,1h,96%P4503A4,CYP2C9N53~5h,41Lh-1,80%,13%,41%,,[13-14]22肺动脉高压患者380mg,43%,3,20mg,113ngmL-1(20~80mg,tid)20%~50%[14]23特殊人群(65),,,40%(Ccr30~80mLmin-1),(Ccr30mLmin-1),(Child-PughAB)[14~15]331单独用于治疗肺动脉高压2005Galie(SildenafilUseinPulmonaryArterialHypertension,SUPER)278()(20,4080mg)126min(6-minutewalkingdistance,6MWD)[45m(+13%),46m(+133%)50m(+143%)]3(meanpulmonaryarterypressure,mPAP)(P=004,P=001,P0001)](PVR)(P=001,P=001,P0001)2011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.1722280mg9,6MWD51m,(NewYorkHeartFunctionAssessmen,tNYHA)(WorldHealthOrganization,WHO),[5],(cardioindex,CI),,Borg,(BNP),,[6-7,16-22],(survivalrate,SR)[7,20]2005(FDA)[23],,[17,24-26]2007NaveenGarg,44(PAP70mmHg,517%IPAH483%)(125mgtid300mgd-1)NYHA6MWD,mPAPPVRPVR/(SVR),CI,,,150mgd-1[25]Singh[26]20(10IPAH10)[7]6020mg,tid16,6MWD[(392139135)m(467228038)m;P0001],mPVR[(1528812)(1499788)mmHgminL-1(WoodUnit);P=002],(mCO)[(239090)(275092)Lmin-1m-2,P=0006],[(9144754)%(9411428)%;P=0002],1(633%947%,P=003)[7](1)32联合治疗,5NO321Wilkens[27]5IPAH:mPAP[(9413)mmHg(6411)mmHg,P005(13814)mmHg(9413)mmHg,P0009],,,Ghofrani[28],,,NYHA3PVR,6MWD1,,,Borg[29]16,267(IPAH,,,2011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.18(20mg,tid,41,20mg40mg,80mg,tid),97%16,6MWD288m(95%CI,139~438m,P0001),mPAP-38mmHg(95%CI,-56~-21mmHg),CO09Lmin-1(95%CI,05~12Lmin-1),,(00620195,P=0002),,Borg,[29]Stiebellehner3,6MWD,mPAPPVR,[30]PVR(31%),3MWDNYHA,[31]TRIUMPH(DoubleBlindPlaceboControlledClinicalInvestigationIntotheEfficacyandTolerabilityofInhaledTreprostinilSodiuminPatientsWithSeverePulmonaryArterialHypertension),2353[NYHA(98%),6MWD200~450m],(54g)4,12,,,Borg[32]322(endothelinreceptorantagonists,ERA),2193,3,3,3696MWD,,NT-ProBNP,NYHA,6MWD(21m8m,P=048),(29%-18%,P001)[33],,3NO(25mg),[34]IPAH106,6MWD[35]323Lepore9IPAH50mgNO,PAPPVR,[36]140,NYHA,,,,,,[37]3,[38]33西地那非在小儿科中应用[39-43],,2011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.19,,(sPAP)PAP,,PAP[40]Raposo-Sonnenfeld[41]6MWDWHO,,(129)6MWD,NYHA,,mPAP,,[42],Raja,(intensivecareuni,tICU)10NO4h1(,05mgkg-11mgkg-115mgkg-120mgkg-1),60min:PAP,;20mgkg-1,;4,,4h05mgkg-14h20mgkg-1[43]4SUPER,FDA(EuropeanAgencyfortheEvaluationofMedicinalProducts,EMEA)20mg,tid,po[5],(40~80mg,tid),225mgd-1[24]20mg,tid,po,21,(80mg,tid)(,),Huddleston03~8mgkg-1d-1,[39]5,SUPER20mg(46%,39%)(13%7%)(10%4%)(9%1%)[5](ED),(,,),,(nonarteriticischemicopticneuropathy,NAION),[5]PDE6[8,14](,Peyronie),,,,,[14],PDEI5ED[44]62011191ClinicalMedicationJourna,lJan2011,Vo.l9,No.110P450CYP3A42C9,,,CYP3A4,[14]PDEI5,,,,,,[1]MclaughlinVV,ArcherSL,BadeschDB,eta.lACCF/AHA2009expertconsensusdocumentonpulmonaryhypertension:areportoftheAmericanCollegeofCardiologyFoundationTaskForceonExpertConsensusDocumentsandtheAmericanHeartAssociation:developedincollaborationwiththeAmericanCollegeofChestPhysicians,AmericanThoracicSociety,Inc,andthePulmonaryHypertensionAssociation[J].Circulation,2009,119:22502294.[2]SandovalJ,BauerleO,PalomarA,eta.lSurvivalinprimarypulmonaryhypertension.Validationofaprognosticequation[J].Circulation,1994,89:17331744.[3]DA'lonzoGE,BarstRJ,AyresSM,eta.lSurvivalinPatientswithPrimaryPulmonaryHypertension[J].AnnalsofInternalMedicine,1991,115:343349.[4]JingZC,XuXQ,HanZY,eta.lRegistryandsurvivalstudyinchinesepatientswithidiopathicandfamilialpulmonaryarterialhypertension[J].Chest,2007,132:373379.[5]GalieN,GhofraniHA,TorbickiA,eta.lSildenafilcitratetherapyforpulmonaryarterialhypertension[J].NEnglJMed,2005,353:21482157.[6]WongRC,KohGM,ChoongPH,eta.lOralsildenafiltherapyimproveshealth-relatedqualityoflifeandfunctionalstatusinpulmonaryarterialhypertension[J].IntJCardio,l2007,119:400402.[7]XuXQ,JingZC,ZhangJH,eta.lTheefficacyandsafetyofsildenafilinChinesepatientswithpulmonaryarterialhypertension[J].HypertensRes,2009,3