临床药学

,,,,,,(,210002):(digoxin2likeimmunoreactivesub2stances,DLIS)(FPIA,TDx)15(DLIS)12,(FPIA)(/FPIA),DLISTDx0.26nmolL-1,DLIS46.7%(7/15),(0.261.52)nmolL-1,(0.550.44)nmolL-1;1DLIS1.52nmolL-1(0.790.48)(0.412.10)nmolL-1;(1.310.80)nmolL-1,(1.050.64)nmolL-1(P0.01)DLIS(0.260.19)(0.070.76)nmolL-1DLIS;,:;;;;;:R969.1:A:1001-2494(2003)10-0782-03:(No.39670843)(19972201):,,,,Tel:[phone]E2mail:[e-mail]fdigoxin2likeimmunoreactivesubstancesinserainthetherapeuticdrugmonitoringLIJin2heng,CAOXiao2mei,CAIMing2hong,RUIJian2zhong,NILi,CHENXiao2ming,GUOLian2qing(De2partmentofClinicalPharmacology,GeneralHospitalofNanjingArmedForces,Nanjing210002,China)ABSTRACT:OBJECTIVETodeterminedirectlyandcalculateindirectlytheconcentrationsofdigoxin2likeimmunoreactivesub2stances(DLIS)inseruminthepatientswithcardiacinsufficiency.METHODSTheapparentdigoxinconcentrationsinserumwerede2terminedin15inpatientswithcardiacinsufficiencywithoutreceivingdigoxinbyfluorescencepolarizationimmunoassay(FPIA)withTDxanalyser.TheconcentrationsofserumDLISintwelvepatientswithcardiacfailurewerecalculatedafterdeterminationsoftotaldigoxinbyFPIAandfreedigoxinbyultrafiltrationwithFPIA.ThelowestmeasureblelevelforFPIAwithTDxanalyserwas0.26nmolL-1.RESULTSInthepatientswithcardiacinsufficiencynotreceivingdigoxin,thepositiveratiofordeterminationofDLISwas46.7%(7in15cases),anditsmeanserumconcentrationwas(0.550.44)nmolL-1(range0.261.52nmolL-1).Inthepatientswithcardiacfailurereceivingdigoxintherapy,thefreedigoxinconcentrationinserumdeterminedwas(0.790.48)(0.412.10)nmolL-1.Thetotaldigoxinconcentrationdetermined(1.310.80nmolL-1)wassignificantlyhigherthanthecalculatedtotaldigoxin(1.050.64nmolL-1)(P0.01).ThecalculatedDLISconcentrationwas(0.260.19)(0.070.76)nmolL-1.TheresultssuggestedthepresenceofelevatedDLISinserumforthesepatientsaboveandwerewellconsistentwiththatobtainedbyrecentlypublishedmethodofDasguptaetal.CONCLUSIONTherearecertainincreasedconcentrationsofDLISinseraofthepa2tientswithcardiacinsufficiency,suggestingthatdigoxinlevelsmeasuredbyimmunoassaymethodmustbeinterpretedcarefullyinthesepatientsaftertreatmentwithdigoxinorotherdigitalispreparations.KEYWORDS:digoxin2likeimmmunoreactivesubstances;fluorescencepolarizationimmunoassay;digoxin;serumdrugconcentration;ultrafiltration;freedrug;ultrafiltration,,,(,),,(digox2in2likeimmunoreactivesubstances,DLIS)[1]DLIS,287ChinPharmJ,2003October,Vol.38No.102003103810©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,DLIS[23],,[4],DLIS,DLIS,11.1(TDx),,(AbbottLaboratories,USA)0,0.64,1.28,2.56,3.846.40nmolL-1;0.96,1.924.48nmolL-11.21.2.1DLIS15,14,16087,(69.86.9)(10),(3),(1),(1),(NYHA,),,12mL,DLIS()4TDx(fluores2cencepolarizationimmunoassay,FPIA),,DLIS1.2.2DLIS12()(2),po62.5250g()FPIA,2FPIA:Dasgupta[5][6]350L(Ultrafree-MC,PLTK,30103,Millipore,USA),(253)(6000g,15min)200L,DLIS:[2,6]25%,75%,:(nmolL-1)=(nmolL-1)/0.75DLIS(nmolL-1)=(nmolL-1)-(nmolL-1)1.3…xs,t22.1DLISTDx0.26nmolL-1DLIS,15DLIS46.7%(7/15),(0.550.44)nmolL-1(0.261.52nmolL-1),1DLIS1.52nmolL-111DLIS(FPIA,TDx)Tab1TheconcentrationsofDLISinthepatientswithcardiacinsufficiency(FPIA,TDxanalyser)/1)DLIS/nmolL-11730.262870.323660.264620.365690.266760.407750.458660.269680.5510741.5211730.2612600.2613610.2614710.2615660.26:1)Note:1)clinicaldiagnosisforprimarydisease2.2DLIS12(0.790.48)(0.412.10)nmolL-1;(1.310.80)nmolL-1,(1.050.64)nmolL-1,(P0.01),DLIS;DLIS(0.260.19)(0.070.76)nmolL-1,22DLIS.nmolL-1Tab2Determinedfreeandtotaldigoxin,calculatedtotaldigoxinandDLISconcentrationsinserumintwelvepatientswithchroniccardiacfailurereceivingdigoxin.nmolL-1DLIS10.460.680.610.0720.861.281.150.1330.550.900.730.1740.911.571.210.3650.580.970.770.2060.681.100.910.1970.581.130.770.3680.540.870.720.1591.262.051.680.37100.510.780.680.10112.103.562.800.76120.410.870.550.32…x0.791.311.051)0.26s0.480.800.640.19:1),P0.01Note:1)P0.01vsdeterminedtotaldigoxinconcentration3DLIS,3872003103810ChinPharmJ,2003October,Vol.38No.10'1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.1000[5]DLIS,DLISNa+2K+2ATPDLIS[7]DLIS,FPIATDx,TDx0.256nmolL-1DLIS,DLIS():13.6%(3/22),0.28(0.260.32)nmolL-1;(34d)83%(34/41),0.55(0.2561.28)nmolL-1;(6)60%(15/25),0.717(0.2561.664)nmolL-1DLIS24%(4/17),100%(19/19),0.256nmolL-1[89],DLIS0.26nmolL-1;15DLIS(0.550.44)nmolL-1,DLIS:DLIS58.3%(7/12),0.45nmolL-1(0.310.66nmolL-1)[3],,,DLIS(0.260.19)(0.070.76)nmolL-1,Dasgupta[10],DLIS(0.250.13)nmolL-1,,DLIS(over2estimation),[11],,,DLIS,,,,[1].[J].,1995,11:256.[2]DasguptaA,SaldanaS,HeimannP.Monitoringfreedigoxinin2steadoftotaldigoxininpatientswithcongestiveheartfailureandhighconcentrationsofdigoxin2likeimmunoreativesubstances[J].ClinChem,1990,36:2121.[3]FrisoloneJ,SylviaLM,GelwanJ,etal.False2positiveserumdi2foxinconcentrationsdeterminatedbythreedigoxinassaysinpa2tientswithliverdisease[J].ClinPharm,1988,7:444.[4]NanjiAA,GreenwayDC.Falselyraisedplasmadigoxinconcen2trationsinliverdisease[J].BrMedJ,1985,290:432.[5]ValdesRJr,GravesSW.Proteinbindingofendogenousdigoxin2immunoactivefactorsinhumanserumanditsvariationwi