左氧氟沙星在大鼠体内的时辰药动学

CN341206R,ISSN10092501Email:[e-mail]2007Jan;12(1):90-9220060913收稿20061013修回李晓天,男,博士,副教授,硕士生导师,主要研究方向:药物动力学Tel:037167781889Email:[e-mail]左氧氟沙星在大鼠体内的时辰药动学李晓天1,王红娟1,王天奎2,王素军31郑州大学药学院,郑州450000,河南;2河南电力医院,郑州450000,河南;3军事医学科学院,北京100000:研究左氧氟沙星在大鼠体内的时辰药动学:大鼠不同时间口服给予左氧氟沙星20mgkg后,采用反相高效液相色谱法测定其血浆药物浓度,并求算其药动学参数:大鼠分别于8001600及2400给药后,其主要药动学参数:Cmax分别为2.372.02和2.85mgL;tmax分别为0.560.50和0.62h;AUC0-分别为11.239.89和11.77mg!h!L-1;t12分别为4.233.51和4.46h;CLs分别为0.390.57和0.36L!kg-1!h-1其各时间点主要药动学参数无统计学差异:左氧氟沙星在大鼠体内的药动学没有明显的时间节律性变化左氧氟沙星;高效液相色谱法;药动学;时间节律:R969:A:10092501(2007)01009003(levofloxacin),,DNA(∀),DNA,[1~4],,,,,,11.1(,99.7%);(,,99.1%);;;1.2Wistar,220~250g,,,:4101521.3LC2010HT,SPD10Avp,,,,LCsolutionversion2.04SulH31.4:C18,5m,150mm#4.6mm(Alltech,),-=2080(vv),0.03molL,pH3.5,299nm,:1mLmin,:25∃1.5,,100gmL,,,50gmL1.6,3500rmin10min,,-20∃0.2mL,20L,1.5mL,3min,4000rmin10min,1.0mL,100L,10000rmin10min,20L1.718,3,6!90!,,12h8001600240020mgkg,10203060120240360480720min,0.45mL,%&1.83P87,22.1,299nm,,5.1min6.9min(1)2.20.2mL,,0.050.10.51.02.05.0gmL,%&,,(AS)(AIS)(Y),(C),:Y=0.2019C+0.0311(r=0.9995)1A:大鼠空白血浆;B:空白血浆加左氧氟沙星及环丙沙星色谱图;C:受试大鼠服药后血浆加内标;1:氧氟沙星;2:环丙沙星内标2.30.051.05.0gmL,,%&0.051.05.0gmL,,,,3(n=5)85%(1)2.4RSD0.051.05.0gmL,%&,RSD5dRSD,3RSD15%,(1)2.520mgkg,,3P87,(2),16008002400,8002400,,(P0.05),1(x∋s,n=5)(gmL)(%)RSD(%)0.0587.9∋7.58.713.11.091.4∋8.66.510.35.092.3∋6.14.47.82(x∋s,n=6)80016002400t12(h)4.2∋0.43.5∋0.34.5∋0.4tmax(h)0.56∋0.210.50∋0.260.62∋0.28Cmax(mgL)2.4∋0.42.0∋0.32.8∋0.4AUC0-t(mg!h!L-1)10.9∋2.89.3∋2.511.5∋3.1AUC0-(mg!h!L-1)11.2∋3.09.9∋2.011.8∋2.5CLs(L!kg-1!h-1)0.39∋0.160.57∋0.180.36∋0.19!91!2007Jan;12(1)3[5],,pH3.5,299nm,,,,,,,,,,[6],,7h,,,;,,HPLC,(80016002400),,4h,7h,,1DjabaroutiS,BoselliE,AllaouchicheB.Determinationoflevofloxacininplasma,bronchialveolarlavageandbonetissuesbyhighperformanceliquidchromatographywithultravioletdetectionusingafullyautomatedextractionmethod[J].JChromatogrB,2004;799:165-172.2ChengFC,TsaiTR,ChenYF,etal.Pharmacokineticstudyoflevofloxacininratbloodandbilebymicrodialysisandhighperformanceliquidchromatography[J].JChromatogrA,2002;961:131-136.3NeckelU,JoukhadarC,FrossardM,etal.Simultaneousdeterminationoflevofloxacinandciprofloxacininmicrodialysatesandplasmabyhighperformanceliquidchromatography[J].AnalChimActa,2002;463:199-206.4,,.[J].,2001;36:834-837.5,.HPLC[J].,2005;36:291-293.6,,.[J].,2003;23:395-396.ChronopharmacokineticsstudyoflevofloxacininratsLIXiaotian1,WANGHongjuan1,WANGTiankui2,WANGSujun31ColleageofPharmacy,ZhengzhouUniversity,Zhengzhou450000,Henan,China;2HenanElectricPowerHospital,Zhengzhou450000,Henan,China;3AcademyofMilitaryMedicalSciences,Beijing10000,ChinaABSTRACTAIM:Tostudythechronopharmacokineticsoflevofloxacininrats.METHODS:Afterlevofloxacinwasorallygiventoratsatdifferenttimes,theconcentrationsoflevofloxacininplasmaandurineweredeterminedbyHPLCandthepharmacokineticsparameterswerecalculated.RESULTS:Themeanpharmacokineticparametersoflevofloxacinat800,1600and2400wereCmax2.37,2.02and2.85mgL;tmax0.56,0.50and0.62h;AUC0-11.23,9.89and11.77mg!h!L-1;t124.23,3.51and4.46h;CLs0.39,0.57and0.36L!kg-1!h-1,respectively.Themainpharmacokineticparametersshowednosignificantdifferencebyoraladministrationat800,1600and2400.CONCLUSION:Therewasnoobviouschangeincircadianrhythmsoflevofloxacininrats.KEYWORDSlevofloxacin;HPLC;chronopharmacokinetics;circadianrhythms本文编辑:李娟!92!ChinJClinPharmacolTher2007Jan;12(1)