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1、生物技术药物的药代动力学特点及检测广州蓝韵医药研究有限公司专注于中药新药临床前研究，保健品研发Cumulative Reve nu esof Selected Biotech no logy Companies (Amgen, Genentech, Chiron, Gen zyme a nd Bioge n)Selected Blockbuster ProteinPharmaceuticalsTWwprmicCompaavPv 4MtUiiirterw (lr%wHi|rv/Ml. ZI1卜 1 a1006(InS1034(Ail matlMj072X4toXal|lraMlbXlulUplc
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3、71IfMfa-A ! RolxHirMi*-ltwrfKW (d PCC 4CM- (V)IMGMid1906SclwiPhwh2714478GCZcAircMMaaii BStsnuLMlum cif EEcf, prwtairn18* and 2002Rodw1102443l0G-C3TSibbmiUi luai al Amolxy iDcioarvion1991Airicb1400IXX)b.yvhrMtlr|ie l Fwcv pr- iir-nOUUVlaes兀ADMccti4?X.lIiMi! M 1C651029“ 1Vy |0趁XIdEAJ/ Cytochrome C/ In
4、ulin fFUdR02468101214161820Molecular Weight kDaIFN alfa-2蛋白肽类药物吸收非肠道给药(Parenteral Route)： IVM=SC=IP鼻腔肺 直肠回肠阴道 颊 口服鼻腔给药(Intranasal administration); In hale admi nistrati on; 口服给药(Oral administration ) Peroral administration经皮给药(Transdermal administration);其他给药途径：结肠、回肠、子宫、阴道、颊、 眼睛等。IM和SC给约生物利用度IM Admi
5、nistratio nDrugBioavailability (%)Alefacept63Interfero n alpha-2a80Triptorelin83SC Administrati onDrugBioavailability (%)Anakinra95Cetrorelix85Darbepoeti n37Follitropi n66Gan irelix91Interferon beta lb50Teriparatide95Pharmacokinetics of IM ADI-SS PEG 20,000 mw in humans with hepatocellular carcinoma
6、AF-eseR G9bx L 5Ttnc |dovv)Intranasal administration易给药；鼻粘膜上皮细胞有犬量的微绒毛和广泛 分布的血管淋巴管；无肝首过效应；伪首过效应(Pseudofirstpass effect):名肽、 蛋白酚(主要是氨肽酶)； calcitonin, oxytoxim LHRH growth hormon巳 interferone, vaccines； 分了届ud to 2 KDa: Dharmacoloqicallv acitive；血脑屏障：IGF1。Inhalation administration Ease of administratio
7、n large surface area (75 m2) High vascularity Bypass of first-pass metabolism Insulin for Type II diabetes Dornase-alpha for cyctic fibrosis Proteases in the lung Local effectsEffect of molecular weight?Plasma bioavailability of therapeuticpeptides versus MW after pulmonaryadministrati onMW (Daltons
8、)H2e-ac- s.LMld UOAOOnoOral administration Generally not therapeutically active; Factors for lack of systemic bioavailability: high gastrointestinal enzyme activity gastrointestinal mucosa as an absorption barrier; cytochrome P450 3A and p glycop rotein activity Available oral forms: cyclosporine (30%) and desmopressin (0.16%);Absorption enhancers; encapsulation in microparticles or nano particles 蛋白肽类药物的分布分布容积小：0.04-0.2 L/kg vs. 1-20 L/kg(小分 子)；分子最大；水溶性大；蛋口结合率高？中央室(Vc):3-8 L=plasma volume和平衡室 (Vss): 14-20 L|ixlCIpiw wrIbiLmiiibIlh)Vd (mUJ” (Clll. pgllpg(n-5)Mean SD83j
