單次和多次給藥對拉西坦人體藥代動力學研究

單次和多次給藥對拉西坦人體藥代動力學研究

utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.utilization.uticicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicicici奧芬泰米爾（4-hy-2-奧爾德信息來源于光的接收，可以采取適當?shù)拇胧?，學習和內存可能低于分配的明確規(guī)定。接受接受和儲存的微芯片。二級和三級微芯片。AHPLCmethodwithexcellentsensitivity,specificityandprecisionwasdevelopedandsuitablyusedfordeterminingtheserumconcentrationofoxiracetamanditspharmacokineticsafterintravenoussingledoseof2000mganddailydoseof2000mgfor7din10healthyChinesevolunteerswerestudiedandevaluated.Thepharmacokineticsparametersofoxiracetamaftersingleandmultipledoseswerenotsignificantlydifferentandtherewasnoaccumulationinserumaftermultipleintravenousadministration.u2004范圍Waters515-2487HPLCwasusedtoseparateanddetectoxiracetaminhumanserum;LXJⅡhighspeedcentrifuge,CX-250superwavecleaner,andAX205Meteller-ToledoscaleweresuppliedbyAmericanAgillentCompany,theShanghaiAnalysisInstrumentFactory,andMetteler-ToledoInstrument(Shanghai)Co.Ltd.,respectively.Theoxiracetamstandard,99.8%,wasfromNationalInstitutefortheControlofPharmaceuticalandBiologicalProducts;Acetoniltrile;spectrumgrade,fromSigmaCompany.TheseparationwascarriedoutwithastablephaseofKromasilNHGivenamountofoxiracetamstandardwasdissolvedinmobilephaseand1.0mg·mLThemixtureof0.5mLserumwith1.0mLacetoniltrilewasvortex-mixedfor2minandcentrifugedat12000r·minUnderabovechromatographicconditions,oxiracetamwaselutedat8.46min.Thechromatogramsofoxiracetamstandard(A),blankserum(B),blankserumspikedwithoxiracetam(C)andvolunteersamples(D)areshowninFigure1.Aliquorof0.5mLblankserumwasmixedwithagivenamountofoxiracetamstocksolutionandastandardcurvewiththerangeof2-100μg·mLTherecovery,intra-dayandinter-dayRSDobstainedbyanalyzingblankserumcontaining5,20,100μg·mLTenChinesehealthyvolunteers,halfmaleandhalffemale,areinvolvedinthisstudy.Theywerefreefromsignificantcardiac,hepatic,renal,pulmonary,neurologic,gastrointestinalandhematologicdiseases,asassessedbyphysicalexamination,electrocardiographyandlaboratorytests.Allvolunteerswerenotpermittedtocomsumealcoholfor72hbeforeorduringthestudyandaskedtoabstainfromanymedicationforatleast1weekbeforeandduringthestudy.Thosewhohadahistoryofdrugoralcoholabuseorallergytothecomponentsofoxiracetaminjectionandthosewhohadconcomitantdrugtherapyofanykindareexcluded.Assignmentofsubjectnumbersanddosinggroupswererandomlydeterminedinadvance.Atwo-waycrossoverdesignwascarriedout.Asingledoseof2000mgofoxiracetamdissolvedin250mL0.9%NaClinjectionwasintravenouslyinfusedinaconstantinfusionratewithaivflowregulatorinexactly30min.Aliquorof5mLvenousbloodwascollectedandtransferredintoachilledtubejustbefore(0h)andat0.25,0.5,1.0,1.5,2,2.5,3,4,6,8,10and12hafterthestartofoxiracetaminfusion,centrifugedwithin10minsampling.Serumwastransferredintotwopolypropylenetubesandkeptat-20℃foranalysis.Afterone-weekwashoutperiod,2000mgofoxiracetamwith250mL0.9%NaClinjectionwasinfusedat7.00amfor7d,andbloodsampleswerecollectedat7.00amfrom5thto7thdbeforeandadministrationsameassingledosedesign.ThepharmacokineticparametersofoxiracetamwerecalculatedbyDrugandStatisticprogram(version1.0,StatisticalSolutions,SunRui-Yuan),thetwo-tailedeinravenusoperationblot,kh-pch-pct的方法,主要見表3.ThemeanserumconcentrationsofoxiracetamaftersingleandmultipleintravenousadministrationareshowninTable2.Thetime-concentrationcurvesareshowninFigure2.ThemeanpharmacokineticparametersofoxiracetamaftersingleandmultipledosesareshowninTable3.lyindex,meh,kh.案例過渡時期Theserumconcentrationofoxiracetamreachedthemaximumafter30minofsingleormultipleintravenousinfusionandthendeclinedrapidlywithin3-4h.Themeanresidencetime,anindicationoftheaveragepersistencetimeofdrugmoleculesinhumanbody,differsignificantlybe