蛋白多肽类药物体内药代动力学特征及分析方法研究进展

PharmaceuticalBiotechnology2014214363～366*210009、。、、、。、、。、、LC-MS/MS、、。Q516A1005-8915201404-0363-04、、、1。。1、。1.1给药途径iv、sc、im。II2。。、。CellpenetratingpeptidesCPPsHIV-1TatPene-tratinandOligoar-Ginine。Penetratin-1GLP-15%3。1.2体内分布。ＲGD4。Phagedisplaytechniques-5。Vd1%～10%0.1%6。mPEG-SC20k-HM-3SDVd0.11L/kg、、、、0.5%～5%7。1.3代谢与消除P450、。。Target-mediateddrugdispositionTMDD8。CEATMDD7dCEACEA10CEACEA9。363*2013-11-012014-02-24863“”No.2012AA020304“AP25”SBY201020063“PEGHM-3”No.CXZZ11_0821。[e-mail]。*Tel/[e-mail][e-mail]。214T1/2βHM-31820T1/2β20min。PEG、FcT1/2β10-11。HM-3PEGT1/2β20h7。1.4排泄。。AP252525.9、、36h0.1%12。1.5其他1.5.1非线性药代动力学特征、、。、、rh-sc-uPAT1/2β613±118min1115±211min1213±219minAUCivCLS13。1.5.2血浆蛋白结合率较高。、14。HM-3AP2570%。2、、。、、LC-MS/MS。2.1酶联免疫吸附测定ELISAELISA。-、、、。EMEA2007。ELISA。Ding15HAS-BNP2BNPHAS。。-ELISAβ-HCG0.1ng/mL16。ELISAAP25。ELISAAP2520ng/mL97.98%～101.07%12。ELISADNAＲT-PCＲDNA。PCＲ3～417。ELISA。HPLCLC-MSELISA。ＲobertELISA2DLC/MS-1GLP-1、GLP-1N、GLP-1CGLP-118。2.2放射性同位素示踪技术、、。125I3H125I。19T125IADWX-1125I-ADWX-1。96.77%。、SDS-PAGE、HPLC。125I-NGF125I-NGF、、20。2.3液相色谱-质谱联用技术LC-MS/MS-LC-MS/MSHPLCMS。ESIMALDI“”21。Liu45YNWNSFGLＲF-NH254-。46NWNSFGLＲF-NH25422。。AliciaSPE-HPLC-MS/MS23。2μm105kPaUPLCUPLC-MSPhylloseptinPSN-182%24。2.4活体成像技术Livinganimalimagingtechnology463。2.4.1核素活体成像技术PETSPECT。PETSPECT。Kamei68Ga-DOTA-insulinPETInsulin-CPPs。CPPs、25。2.4.2荧光标记技术、。FITC-BSAFITC-BSA。FITC-BSA26。2.5新型分析技术2.5.1电化学发光免疫分析ECLIAECLIAElectro-chemiluminescenceImmunoassay。Ｒubpy32+AbAg-AbＲubpy32+Ag-Ab。LoweＲanibizumab300pg/mL27。ECLIA、ELISALC-MS/MSPEG2.09～1258.52～75100～1000ng/mLECLIA28。2.5.2微流控芯片免疫分析方法。、、。Lin29PDMS4pmol/L。GyrosTM。LiuGyrosTMGyrosTM、ELISA30。3。、、。。、、、。ELISA。ELISA。、、。。6～81HPLC。。LC-MS/MS。、。LC-MS/MS、、。、、。、、、、。1XuHMYinＲTChenXHetal．AnＲGD-modifiedendostatin-derivedsyntheticpeptideshowsantitumoractivityinvivoJ．BioconjugateChem200819101980.2Alcala-BarrazaSＲLeeMSHansonLＲetal．IntranasaldeliveryofneurotrophicfactorsBDNFCNTFEPOandNT-4totheCNSJ．DrugTarget201018179.3KhafagyESMorishitaMKameiNetal．Efficiencyofcell-pene-tratingpeptidesonthenasalandintestinalabsorptionoftherapeu-ticpeptidesandproteinsJ．InterJPharmac200938149.4LiuS．ＲadiolabeledcyclicＲGDpeptidesasintegrinαvβ3-targe-tedradiotracersmaximizingbindingaffinityviabivalencyJ．BioconjugChem2009202199.5WanXMChenYPXuWＲetal．Dentificationofnose-to-brainhomingpeptidethroughphagedisplayJ．Peptides200920243.6CaiYZhangZFanFetal．Harmacokineticstissuedistribu-tionexcretionandantiviralactivityofpegylatedrecombinanthumanconsensusinterferon-alphavariantinmonkeysratsand563214guineapigsJ．ＲegulPept17374．7．PEGHM-3J．药物生物技术2011185416.8LuuKTBergqvistSChenEetal．Amodel-basedapproachtopredictingthehumanpharmacokineticsofamonoclonalantibodyexhibitingtaret-mediateddrugdispositionJ．JPharmacolExpTher2012341702.9UrvaSＲBalthasarJP．TargetmediateddispositionofT84．66amonoclonalanti-CEAantibodyapplicationinthedetectionofcolorectalcancerxenograftsJ．Mabs20102167．10ZalevskyJChamberlainAKHortonHMetal．Enhancedanti-bodyhalf-lifeimprovesinvivoactivityJ．NatBiotechnol201028157．11StorkＲZettlitzKAＲetherMetal．N-glycosylationasnovelstrategytoimprovepharmacokineticpropertiesofbispecificsin-gle-chaindiabodiesJ．JBiolChem20082837804．12LiYBXuHMHuJLetal．Quantitativeanalysisandpharmaco-kineticsstudyofintegrinantagonistAP25inratplasmaJ．Protein＆Peptide．201320584.13．J．药学学报200035293．14BuurJLBaynesＲESmithGWetal．Aphysiologicallybasedpharmacokineticmodellinkingplasmaproteinbindinginterac-tionswithdrugdispositionJ．ＲesVetSci2009126293.15DingYDJiangLChenLYetal．AsandwichELISAforassess-mentofpharmacokineticsofHSA-BNP2fusionproteininmouseplasmaJ．JPharmaceutBiomed201051658.16．间接包被ELISA法检测血清游离β-HCG方法学研究D．2010.17YinHHZhuYYXuLGetal．Ultrasensitivedetectionofmela-minebasedonaDNA-labeledimmunosensorJ．BiosensBioelec-tron20134251．18ＲobertEMArvindGK．Combineduseofimmunoassayandtwo-dimensionalliquidchromatographymassspectrometryforthedetectionandidentificationofmetabolitesfrombiotherapeuticpharmacokineticsamplesJ．JPharmaceutBiomed201053221．19．ADWX-1J．药物生物技术2012194334．20．125I-NGF、J．现代仪器201218110．21ArmandoAＲLudgerSＲZaharenkoAJetal．Combiningmulti-dimensionalliquidchromatographyandMALDI-TOF-MSforthefingerprintanalysisofsecretedpeptidesfromtheunexploredseaanemonespeciesPhymanthuscruciferJ．JChromatogrB201290330.22LiuZFＲenCJonesWetal．LC-MS/MSquantificationofaneuropeptidefragmentkisspeptin-10NSC741805andcharac-terizationofitsdecompositionproductandpharmacokineticsinratsJ．JChromatogrB20139261.23NavarreteAPazMMartínezAetal．SimultaneousonlineSPE-HPLC-MS/MSanalysisofdocetaxeltemsirolimusandsirolimusinwholebloodandhumanplasmaJ．JChromatogrB201392135.24ZhangＲWLiuWTGengLLetal．Quantitativeanalysisofanovelantimicrobialpeptideinratplasmabyultraperformanceliquidchromatography-tandemmassspectrometryJ．JPharma-ceutBiomed201113191.25KameiaNMorishitaaMKanayamabY．Molecularimaginganaly-sisofintestinalinsulinabsorptionboostedbycell-penetratingpeptidesbyusingpositronemissiontomographyJ．JControllＲelease2010146116.26．J．影像科学与光化学2010285354．27LoweJMaiaMWakshullEetal．Developmentofa