生物技术药物药代动力学研究的方法学和实验设计

*汪小凤郑青**(510630)生物技术药物由于自身具有的特点,使得其在体内的药代动力学机制比传统药物更为复杂近年来,对于这类药物在体内的代谢机制的研究日趋增加,研究方法也日趋成熟概述了生物技术药物的药代动力学研究方法以及实验设计的特点生物技术药物药代动力学方法学实验设计:20030916:20031124*863(2001AA215131,2002AA2Z3318),(010424)**,:[e-mail],,,,,,,,,,,,1,,,,,,,[1],,,,,,2,,,242CHINABIOTECHNOLOGY2004221,H3C14S32I125,I125,,,,;,TLodogen[2]I125,[3]I1252b,[4],,,211标记后的放射性比放射性和比生物活性[5](1):,,,,(2):95%I125,98%,,,,,,(3):,,,,(RHPLC)I125,(4):?Harris[6]LodogenTI125;Salacinski[7]LodogenI125,23,,,(ED50),212鉴别标记蛋白质和降解物或代谢产物,,,I125I125I125:(1)SDSPAGE:,,,,,,,,,(2)HPLC:(RHPLC)(SEHPLC0)(IEHPLC)[8],SEHPLC,RHPLC,,22,812:,221放射免疫法(RIA)(Ag),(IAg)(Ab),,[9],rhbFGF222免疫放射定量法(RMA),,IAb,Ab:Ag:IAbAgAb,,,223酶联免疫法(ELLSA)ELLSAIRMA,,HRP,,ELLSA,,,,,[10]ELLSA,,[11](911),,911BSA911HSA,ELISA,911,,,[12]23,,()(),,,[12](rhTNFDa),,24(HPLC),,,,[13](AVM),,(HPCE),,,,,,,100kDa,,3,8224,,,,,,,???,,,,,,,80%,,4,,,,,,HPLC,,,,,,,,,DeSmedt[14]visualFARP,,,,,,,,,[1],..,2001,10(12):884~887[2],,.[M].:,1991,40~41[3],,,.2b.,2001,32(6):457~461[4],,,..,2002,23(12):1065~1067[5],,.[M].:,1999.10[6]HarrisR,FradeLG,CreightoaLJ,etal.LnvestigationbyHPLCofthecatabolismofrecombinanttissueplasminogenactivatorintherats.ThrombHaemostas,1998,60(1):107~112[7]SalacinskiPR,McleanC,SykcesJE,etal.Lodinationofproteinsglycoproteinsandpeptidesusingasolidphaseoxidizingagent,1,3,4,6tetrachloro3,6diphenylglycoluril(lodogen).AnalBlochem,1981,117:136~146[8]LinXW,TangZM.Pharmocokineticsofrecomminbanthumangranalocyoerolotrystimulatingfactorinrabbitsandmice.ActaPharmocologyicasinice,1997,18(1):44[9],,,..,1999,25(3):226~228[10],,,..,2002,16(3):220~222[11],,,..,2003,38(1):23~26[12],,,..,1997,13(1):50~56[13],,..,2002,32(11):8~11[14]DeSmedtSC,MeyvisT,VanOostveldtP,etal.VisualFRAPmethodtostudytransportphenomenaoffluorescentprobemacromolecules.Journalofcontrolledrelease,1996,41(1~2):s7(87)832:StudyontheReproductiveImmunizationonSexingControlinDairyCattlewithFrozenSexedSemenLUOChenghao1JIAFude2MAJunhong2LIUZhuang2(1SouthChinaAgriculturalUniversity,Guangzhou510642,China2TianjinBreedingResearchCentreinDairyCattle,Tianjin300221,China)AbstractThistrialwasproceededinprocessofsemenproductioninthePurebredSireStationtopreparetheFrozenSexdSemenbyuseofReproductiveImmunization,andwasbeingrealizationofSexingControlinDairyCattleincombinationwiththeartificialinsemination.Itsactionprinciple,featuresandapplicationweredescribedchiefly.ItwasfoundthatitispossibleforseparationofXandYchromosomebearingspermusingSucroseSolutionDensityGradientCentrifugationbasedonDNAdifference,anditwasalsoanevidenceofusingFluorescentstainingforinspectationoftheXandYchromosomebearingsperm.HYantigenwasisolatedfrominbredmiceandsubsequentlyusedtoimmunizefemaleratsforpreparingHYantiserumIgG.ItwasalsoanevidencethatusingHYantiserumIgGshowedmarkedspecificinhibitiononYchromosomebearingsperm.ResultsalsoindicatedthattheycouldbereachedthesimilarconceptionrateinestruswiththeFrozenSexedSemenjustasusingwiththenormalfrozensemensimultaneously,butamarkedvariationofsexualityatbirthbetweenthem.Aratioofmorethan607%femaleprogenyincowswassuccessfullyreachedafterartificialinseminationwithFrozenSexedSemenpretreatedwithHYantiserumIgGinabiggroupof117cowsinthistrial.KeywordsReproductiveimmunizationFrozensexedsemenHYantiserumIgGSexingcontol(83)TheMethodologyandExperimentalDegsininPharmacokineticsStudyofBiotechnologicalDrugsWANGXiaofengZHENGQing(BiopharmaceuticalR&DCenterofJinanUniversity,Guangzhou510630,China)AbstractBecauseofthespecialtyofthebiotechnologicaldrugs,itsmechanismofpharmacokineticsismorecomplexthanthetraditionaldrugs.Inrecentyears,researchonpharmacokineticsofbiotechnologicaldrugswasincreasingandthemethodsweredeveloped.Inthisarticle,themethodologyandexperimentaldesigninpharmacokineticsstudyofbiotechnologicaldrugswerediscussed.KeywordsBiotechnologicaldrugsPharmacokineticsMethodologyExperimentaldegsin872: