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1、Zemplar™(paricalcitolinjection)FliptopVialDESCRIPTIONZemplar™(paricalcitolinjection)isasyntheticallymanufacturedvitaminDanalog.Itisavailableasasterile,clear,colorless,aqueoussolutionforintravenousinjection.EachmLcontainsparicalcitol,5mcg;propyleneglycol
2、,30%(v/v);andalcohol,20%(v/v).Paricalcitolisawhitepowderchemicallydesignatedas19-nor-1a,3ß,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-trieneandhasthefollowingstructuralformula:CH3OHHOOHMolecularformulaisC27H44O3.Molecularweightis416.65.CLINICALPHARM
3、ACOLOGYMechanismofActionParicalcitolisasyntheticvitaminDanalog.VitaminDandparicalcitolhavebeenshowntoreduceparathyroidhormone(PTH)levels.PharmacokineticsDistributionThepharmacokineticsofparicalcitolhavebeenstudiedinpatientswithchronicrenalfailure(CRF)re
4、quiringhemodialysis.Zemplar™isadministeredasanintravenousbolusinjection.Withintwohoursafteradministeringdosesrangingfrom0.04to0.24mcg/kg,concentrationsofparicalcitoldecreasedrapidly;thereafter,concentrationsofparicalcitoldeclinedlog-linearlywithameanhal
5、f-lifeofabout15hours.Noaccumulationofparicalcitolwasobservedwithmultipledosing.EliminationInhealthysubjects,plasmaradioactivityafterasingle0.16mcg/kgintravenousbolusdose3ofH-paricalcitol(n=4)wasattributedtoparentdrug.Paricalcitolwaseliminatedprimarilyby
6、hepatobiliaryexcretion,as74%oftheradioactivedosewasrecoveredinfecesandonly16%wasfoundinurine.MetabolismSeveralunknownmetabolitesweredetectedinboththeurineandfeces,withnodetectableparicalcitolintheurine.Thesemetaboliteshavenotbeencharacterizedandhavenotb
7、eenidentified.Together,thesemetabolitescontributed51%oftheurinaryradioactivityand59%ofthefecalradioactivity.Invitroplasmaproteinbindingofparicalcitolwasextensive(>99.9%)andnonsaturableovertheconcentrationrangeof1to100ng/mL.ParicalcitolPharmacokineticCha
8、racteristicsinCRFPatients(0.24mcg/kgdose)ParameternValues(Mean±SD).Cmax(5min.afterbolus)61850±664(pg/mL)-AUC0527382±8230(pg•hr/mL)CL50.72±0.24(L/hr)Vss56±2(L)LaboratoryTestsInplacebo-controlledstudies,paricalcitolreducedserumtota