盐酸特比萘芬片的人体生物等效性研究

1,2,1,1,1,1(1,410078;2,201203)[]::18(0125g),LC2MS/MS:Cmax(941.6196.5)(917.1264.8)gL-1,Tmax(1.380.39)(1.380.61)h,AUC072h(4696.41192.8)(4596.91189.8)ghL-1,AUC0(4838.71188.1)(4755.91183.2)ghL-1F(AUC072h)(989)%:[];;LC2MS/MS[]R969.1;R978.1[]A[]1003-3734(2008)14-1261-03BioequivalenceofterbinafinehydrochloridetabletsinhealthyvolunteersOUYANGDong2sheng1,SHIHui2yan2,TANZhi2rong1,LUOLi2fang1,GUODong1,LIUYing2zi1(1ClinicalPharmacologyInstituteofCentralSouthUniversity,Changsha410078,China;2ShanghaiMedicilonIncorporation,Shanghai201203,China)[Abstract]Objective:Toevaluatetherelativebioavailabilityofterbinafinehydrochloridetablets.Meth2ods:Theplasmaconcentrationsofterbinafinefrom18healthymalevolunteers,whoreceivedasinglecrossoverdoseoftestandreferenceterbinafine0.25g,weremeasuredbyLC2MS/MS.Results:ThepharmacokineticprofilesoftestandreferenceterbinafinewereCmax,(941.6196.5)vs(917.1264.8)gL-1;Tmax,(1.380.39)vs(1.380.61)h;AUC072h,(4696.41192.8)vs(4596.91189.8)ghL-1;AUC0,(4838.71188.1)vs(4755.91183.2)ghL-1,respectively.Therelativebioavailabilityofthetestterbinafinewas(989)%.Conclusion:Thetestterbinafinewasbioequivalenttotherefrenceterbinafine.[Keywords]terbinafinehydrochloridetablets;bioequvivalence;LC2MS/MS2,[1-4],,,,,,,[5-8][9]LC2MS/MS,:(,0.125g,:060101);:,,01125g,:0509010KJ);(:98.5%;:YBH06372006);,,WatersQuattroMicroAPI,(ESI)Masslynx4.0;Waters269518,2027,5376kg,,1621ChineseJournalofNewDrugs2008,Vol.17No.14200817142,,18,,7d;0.25g(0h)0.25,0.5,0.75,1,1.5,2,3,4,6,8,12,24,48,72h5mL,,-20,4.1HypurityC18(150mm2110mm,5m);0.1%2210mmolL-1(206020);0.20mLmin-1;40,154.2ESI+MRM;:3.5kV;:25V;:100;:250;:50Lh-1;:250Lh-14.3200L,600L,2min,13000rmin-1,10min,400L400L0.1%,10L4.4,12.97min,1LC2MS/MS4.5,,:2.72730gL-1,Y=13.1665X+189.469,1/x,(r)0.992,1.3gL-1(2730,85.2,5.4gL-1)5,3d:RSD3.9%,4.8%11.0%,15%;99.7%,89.6%,86.4%;RSD11.0%,5.0%4.7%,15%4.6:2730,85.2,5.4gL-15,,12h,3(P0.05),12h2730,85.2,5.4gL-15,-2028d,(d1)d283d1d28(P0.05),-2028d4.72730,85.2,5.4gL-1,15%DASVer2.0180.25g,222180.25g22621ChineseJournalofNewDrugs2008,Vol.17No.1420081714180.25g,11180.25gAUC072h/ghL-14596.91189.84696.41192.8AUC0/ghL-14755.91183.24838.71188.1Cmax/gL-1917.1264.8941.6196.5t1/2/h18.93.818.13.3Tmax/h1.380.611.380.39Tmax,(U=0.496,P=0.620)AUC072h,AUC0Cmax,,:(P0.05)Cmax,AUC072hAUC0t2thightlowt0.05AUC072hAUC090%AUC072hAUC080%125%;Cmax90%,Cmax70%143%,,,,,,,(Cmax,t1/2,Tmax,AUC0t),[10-11],180.25g,Cmax,Tmax,AUC072hAUC0F(AUC072h)(989)%,t90%,,[](1967-),,,:[phone],E2mail:[e-mail][][1],,.[M].:,2001:991-992.[2].[M].:,2004:458-458.[3],,,.[J].,2006,28(4):6-8.[4].[J].,2004,20(14):1380-1381.[5].[J].,2007,6(2):91-91.[6],.[J].,2007,17(3):178-179.[7],,.163[J].,2007,36(1):56-56.[8],,.67[J].,2006,35(1):73-74.[9],.[J].,2005,25(4):320-322.[10]BALFOURJA,FAULDSD.Terbinafine:areviewofitspharmaco2dynamicandpharmacokineticproperties,andtherapeuticpotentialinsuperficialmycoses[J].Drugs,1992,43(2):259-284.[11]KOVARIKJM,MUELLEREA,ZEHENDERH,etal.Multiple2dosepharmacokineticsanddistributionintissueofterbinafineandmetabolites[J].AntimicrobAgentsChemother,1995,39(12):2738-2741.:/:2007-11-29RequipXL(GSK)(ropinirole,RequipXL)1,,,III,2.1hGSK,,,,1RequipXL,: