生物技术药物的药代动力学特点及检测

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1、优秀精品课件文档资料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CumulativeRevenuesofSelectedBiotechnologyCompanies(Amgen,Genentech,Chiron,GenzymeandBiogen)SelectedBlockbusterProteinPharmaceuticals生物技术药物重组蛋白多肽类单克隆抗体及其片断寡核苷酸疫苗制剂基因治疗药物（核酸制剂）干细胞药物？蛋白肽类药物药代动力学吸收分布代谢与排泄蛋白肽类药

2、物吸收小分子多肽：被动吸收大分子多肽：水溶性：细胞间隙脂溶性：膜脂扩散胞饮淋巴系统吸收：po干扰素；高度脂溶性？影响蛋白肽类药物吸收因素药物稳定性；细胞渗透性：MW1000，鼻粘膜》肠粘膜CorrelationbetweenMWandthecumulativerecoveryofscrINFalpha-2a,cytochromec,inulinand5-fluoro-2-deoxyuridine(FUDR)intheefferentlymphinsheep蛋白肽类药物吸收非肠道给药(ParenteralRoute)：I

3、V>M＝SC＝IP>鼻腔>肺>直肠>回肠>阴道>颊>口服鼻腔给药(Intranasaladministration);Inhaleadministration;口服给药(Oraladministration)Peroraladministration经皮给药(Transdermaladministration);其他给药途径:结肠、回肠、子宫、阴道、颊、眼睛等。IM和SC给药生物利用度IMAdministrationDrugBioavailability(%)Alefacept63Interferonalpha-2a>

4、80Triptorelin83SCAdministrationDrugBioavailability(%)Anakinra95Cetrorelix85Darbepoetin37Follitropin66Ganirelix91Interferonbeta-1b50Teriparatide95PharmacokineticsofIMADI-SSPEG20,000mwinhumanswithhepatocellularcarcinomaIntranasaladministration易给药；鼻粘膜上皮细胞有大量的微绒毛和广泛

5、分布的血管淋巴管；无肝首过效应；伪首过效应(Pseudo－first－passeffect)；多肽、蛋白酶（主要是氨肽酶）；calcitonin,oxytoxin,LH-RH,growthhormone,interferone,vaccines；分子量upto2KDa:pharmacologicallyacitive；血脑屏障：IGF-1。InhalationadministrationEaseofadministrationlargesurfacearea(75m2)HighvascularityBypassoffi

6、rst-passmetabolismInsulinforTypeIIdiabetesDornase-alphaforcycticfibrosisProteasesinthelungLocaleffectsEffectofmolecularweight?PlasmabioavailabilityoftherapeuticpeptidesversusMWafterpulmonaryadministrationOraladministrationGenerallynottherapeuticallyactive;Factor

7、sforlackofsystemicbioavailability:highgastrointestinalenzymeactivitygastrointestinalmucosaasanabsorptionbarrier;cytochromeP4503Aandp-glycoproteinactivityAvailableoralforms:cyclosporine(30%)anddesmopressin(0.16%);Absorptionenhancers;encapsulationinmicroparticleso

8、rnanoparticles.蛋白肽类药物的分布分布容积小：0.04-0.2L/kgvs.1-20L/kg(小分子);分子量大;水溶性大;蛋白结合率高？中央室（Vc):3-8L=plasmavolume和平衡室(Vss):14-20L<2x中央室;蛋白结合:reduceclearance;Site-specificandtarge