剪物性质影响吸收 The Biopharmaceutics classification system(BCS) Class 1: High Solubility-High Permeability generally very well-absorbed compounds Class 2: Low Solubility-High permeability exhibit dissolution rate-limited absorption Class 3: High Solubility-Low Permeability exhibit permeability rate-limited absorption Class 4: Low Solubility-Low Permeability: very poor oral bioavailability
药物性质影响吸收 The Biopharmaceutics classification system (BCS) • Class 1: High Solubility-High Permeability: generally very well-absorbed compounds • Class 2: Low Solubility-High Permeability: exhibit dissolution rate-limited absorption • Class 3: High Solubility-Low Permeability: exhibit permeability rate-limited absorption • Class 4: Low Solubility-Low Permeability: very poor oral bioavailability
消牝道代谢酶的影响 Metabolic enzymes in intestinal tract I glucuronic transfase(葡萄糖醛酸转移酶)结合反应十二 指肠活性最高如黄芩苷的代谢; 2β- glucuronidase(β-葡萄糖醛酸苷酶)使药物的葡萄糖醛 酸结合物水解此酶在肠道活性极高,与许多药物的再利用 重吸收有关。 3 acetyl- transferase(乙酰转移酶)含NH,-OH,-COOH 的药物被乙酰化,形成乙酰化代谢物; 4 methyl- transferase(甲基转移酶)甲基化反应如儿茶酚胺 类药物的OH的甲基化代谢 5 esterase(酯酶)与药物的酯化反应有关,如药物中OH 的酯化阿司匹林的代谢 6 hydroxylase(羟化酶)药物化学结构发生羟化反应,该酶 广泛存在于肠道,与药物解毒密切相关 7 sulfatase(硫酸转移酶)含醇和酚-OH、芳香氨基的药物 活性成分如儿茶酚类的代谢
消化道代谢酶的影响 Metabolic enzymes in intestinal tract 1 glucuuronic transfase (葡萄糖醛酸转移酶) 结合反应 十二 指肠活性最高 如黄芩苷的代谢； 2 β- glucuronidase (β- 葡萄糖醛酸苷酶) 使药物的葡萄糖醛 酸结合物水解 此酶在肠道活性极高，与许多药物的再利用、 重吸收有关。 3 acethyl-transferase (乙酰转移酶) 含-NH，-OH，-COOH 的药物被乙酰化，形成乙酰化代谢物； 4 methyl- transferase (甲基转移酶) 甲基化反应 如儿茶酚胺 类药物的-OH的甲基化代谢 5 esterase (酯酶) 与药物的酯化反应有关，如药物中-OH 的酯化 阿司匹林的代谢 6 hydroxylase (羟化酶) 药物化学结构发生羟化反应，该酶 广泛存在于肠道， 与药物解毒密切相关 7 sulfatase (硫酸转移酶) 含醇和酚-OH、芳香氨基的药物 活性成分 如儿茶酚类的代谢
Dissolution Permeability/Flux Grug Physico-chemical Pharmacokinetic Parameter Parameter Liver Systemic Availability Fig Oral absorption of drugs from a drug product
Fig Oral absorption of drugs from a drug product
paracellular efflux′ transcellular transcellular endocytosis ee(↑⑧ Mm passive carrier mediated specialized Fig gi membrane transport. The transport through the enteroyte barrier can be generally divided into active, passive and specialized transport and into a paracellular and transcellular route
Fig GI membrane transport. The transport through the enteroyte barrier can be generally divided into active, passive and specialized transport and into a paracellular and transcellular route
Metabolite Profiles Scaling In vitro In vitro Factor/In vivo Incubation Clint Rate of drus L iver model LOSS Formation CL In vivo b ody clearance
In Vitro Incubation Metabolite Profiles In Vitro CL int In Vivo CL int F ormation C L L iver model In Vivo Body Clearance R ate of Drug L oss Scaling F actor