药物评价和研究中心申请编号21-849临床药理学与生物药剂学评价ClinicalPharmacologyandBiopharmaceuticsReviewNDA:21-849(SN-000)BrandName:ZegeridGenericName:OmeprazoleDosageformandStrength:20and40mgCapsulesRouteofadministration:OralIndication:RelatedtoGIdisordersSponsor:Santarus,Inc.Typeofsubmission:OriginalClinicalDivision:GIandDermatologyDivisionOCPBDivision:DCPBIIIPriority:StandardSubmissiondate:04/26/05,O1/04/06OCPBConsultdate:OS/10/OSReviewer:Tien-MienChen,Ph.D.Teamleader:EdwardD.Bashaw,Pharm.D.Zegerid临床药理学及生物药剂学评论新药申请:21-849(SN-000)商品名:Zegerid通用名:奥美拉唑剂型及规格:20and40mg胶囊剂给药途径:口服不良反应:肠胃系统紊乱申请者:Santarus,Inc.提交种类:原研临床部:胃肠和皮肤部OCPB部:DCPBIII优先次序:标准提交日期:04/26/05,01/04/06OCPB受理日期:OS/10/OS评审员:Tien-MienChen,Ph.D.组长:EdwardD.Bashaw,Pharm.D.ⅠExecutiveSummaryOmeprazoleisasubstitutedbenzimidazolethatinhibitsgastricacidsecretionviaspecificinhibitionofH+/K+ATPaseenzymesystematthesecretorysurfaceofthegastricparietalcell.OmeprazolehasbeenapprovedandmarketedintheUSsince1989asPrilosecdelayedrelease(DR)20and40mgcapsulesgivenoncedailyforthetreatmentofavarietyofshoal:-andlong-termGIconditions.Prilosecisanenteric-coateddosageformfordelayedreleasepurposeduetotheacid-labilenatureofomeprazole.Santaruspreviouslydevelopedanimmediaterelease(IR)formulationofomeprazolepowderfororalsuspension(Zegerid)comprisedofimmediatereleaseomeprazoleandsodiumbicarbonate,withsodiumbicarbonateprotectingomeprazolefromrapiddegradationbygastricacid.In2004,twodosagestrengthsofZegeridIRpowderfororalsuspension(20mgunderNDA21-636and40mgunderNDA21-706,respectively)wereapprovedintheUSbasedon505(b)(2)provisionrelyingonpharmacokinetic(PK)andpharmacodynamic(PD)bridgingdatatosupportthereferencetotheAgency'spreviousfindingofsafetyandefficacyforPrilosecDR20and40mgcapsules.Ⅰ概要奥美拉唑是一种通过特异性抑制腺体表面的H+/K+ATPase酶系统来抑制胃酸分泌的苯并咪唑替代物。奥美拉唑于1989年在美国被批准并上市销售，奥美拉唑20mg和40mg缓释胶囊治疗一系列的胃肠疾病。洛赛克是基于奥美拉唑对酸不稳定而制作的一种肠溶缓释剂。Santarus先前开发了由奥美拉唑和碳酸氢钠粉末混合而成的奥美拉唑直接释放口服制剂，以碳酸氢钠防止奥美拉唑在胃酸中的快速降解。2004年，ZegeridIR的两个优势剂型，口服悬浮剂（NDA编号为21-636的20mg和NDA编号为21-706的40mg，单独的）在美国基于505(b)(2)规定被批准。其药代动力学和药效学数据支持了之前涉及到管理中心发现的洛赛克20mg和40mg胶囊安全性和有效性的问题。Thecurrentsubmission(NDA21-849)forZegerid20and40mgIRcapsules,alsofiledunder505(b)(2)provisions,consistsoftwoclinicalpharmacologystudies,OME-IR(CAP)-CO1andOME-IR(CAP)-C02,plussupportivestudies.StudyOME-IR(CAP)-COlevaluatedthePKandPDofomeprazolewhenZegeridIR20mgcapsulewasDR20mgcapsulegivenQDfor7days.当前提交(NDA21-849)的Zegerid20mg和40mg胶囊,也是基于505(b)(2)条款，有两种临床药理学，OME-IR(CAP)-CO1和OME-IR(CAP)-C02,加上支持研究。在给予ZegeridIR20mg胶囊给予7天研究其药效学的同时评价了OME-IR(CAP)-CO1药代动力学和药效学。StudyOME-IRgiven1hour-premealQDvs.Prilosec(CAP)-C02evaluatedsimilarlythePKandPDofomeprazolewhenZegeridIR40mgcapsulewasgiven1hour-premealQDvs.PrilosecDR40mgcapsuleQDfor7days.onDay8vs.Zegeridgiven1hour-premealwerealsoinvestigated.ThefoodeffectsonZegeridgiven1hour-postmealonDay7forbothZegeridIR20and40mgcapsulesZegeridIR40mg胶囊与PrilosecDR40mg胶囊在为期7日饭前1小时给药的药效学对比研究中，OME-IR和洛赛克(CA...
