生物技术药物药代动力学特特点及检测.pptVIP

Cumulative Revenues of Selected Biotechnology Companies(amgen, Genentech Chiron Genzyme and Biogen) 12000 10000 s in Million 6000 4000 g00 CP.,...of小 YEAR Selected blockbuster protein Pharmaceuticals Constituent million) (in s million) Epogen Erythropoetri Amgen 2 antibody 上Liy ce-InterFeru and Kanti-HT) Amgen 3430 erythrocyte productlon son/orTho Interferon B- Rhematoid arthritis Centocon Johnson 11 46 Chimeric MAh) snagS Huinanlced MAb Reapiatuy syucyual I MedlmuAbboct E6B 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) 千细胞药物? 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 Correlation between MW and the cumulative recovery of sc rINF alpha-2a, cytochrome c, inulin and 5-fluoro-2 deoxyuridine( FUdr)in the efferent lymph in sheep 百50 IFN-alfa-2a Cytochrome C FUdR 02468101214161820 Molecular Weight (kDa 蛋白肽类药物吸收 非肠道给药( Parenteral route):IM=SC= IP鼻腔肺直肠回肠阴道颊口服 鼻腔给药( Intranasal administration); Inhale administration 口服给药( Oral administration) o 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给药生物利用度 Administration Administration D Bioavailability Drug Bioavailability (%) Alefacept 63 Darbepoetin Interferon80 Follitropin Ganirelix alpha-2a Interferon beta-50 1b Triptorelin 83 Teriparatide95 Pharmacokinetics of IM ADi-SS PEg 20, 000 mw in humans with hepatocellular carcinoma Time (days) Intranasal administration 易给药;鼻粘膜上皮细胞有大量的微绒毛和广泛 分布的血管淋巴管;无肝首过效应; 伪首过效应( Pseudo-frst- pass effect);多肽、 蛋白酶(主要是氨肽酶) o calcitonin, oXytoxin, LH-RH growth hormone , interferone vaccines 分子量upto2KDa: pharmacologically acitive 血脑屏障:IGF-1。