第五章_药物代谢080730ppt.ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * LOGO activity decreased 氯丙嗪→去甲氯丙嗪 LOGO activity increased 解热镇痛药非那西丁→对乙酰氨基酚 LOGO activation 左旋多巴酶解脱羧→多巴胺 LOGO toxicity 异烟肼→乙酰肼 C-N-NH 2 H O N N O H C-N-N H - C-CH 3 O N O C-OH + O H C-N-NH 2 CH 3 - Hepatotoxicity 肝毒性 Mutagenicity 致突变 Teratogenicity 致畸变 Carcinogenicity 致癌 LOGO O = C NH-CO NH-CO C CH 2 CH 3 CH 2 CH 2 CH CH 3 CH 3 CH 3 CH 3 CH 2 CH 2 C CH 2 CH 3 C NH-CO NH-CO O = C OH (异戊巴比妥)　　　　 　(羟化异戊巴比妥) Alkyl group ---- alcohol LOGO CH 3 SO 2 NHCONHC 4 H 9 [ O] SO 2 NHCONHC 4 H 9 CH 2 OH [ O ] SO 2 NHCONHC 4 H 9 CHO [ O ] SO 2 NHCONHC 4 H 9 COOH Aromatic ring ---- phenol 降糖药甲苯磺丁脲 LOGO Oxidation at S or N S N CH 2 CH 2 CH 2 N CH 3 CH 3 Cl Cl CH 3 CH 3 CH 2 CH 2 CH 2 N N S O S N CH 2 CH 2 CH 2 N CH 3 CH 3 Cl O LOGO Monoamineoxidaze CH 2 CHCH 3 NH 2 CH 2 CHCH 3 [O] O +NH 3 苯丙胺→苯丙酮 LOGO Esters --- alcohol and acid aspirin to salicylic acid COOH OCOCH 3 OH COOH +CH 3 COOH LOGO Amides to amine and acid 非那西丁→对乙氧基苯胺 OC 2 H 5 NHCOCH 3 NH 2 OC 2 H 5 +CH 3 COOH LOGO Glucuronidation 醚型结合 酯型结合 O COOH O UDP OH OH HO + NHCOCH 3 OH HO OH OH O- COOH O NHCOCH 3 + UDP COOH OCOCH 3 + UDPGA OCOCH 3 COO GA + UDP LOGO Sulfate 羟基结合 氨基结合 NHC-CH 3 O OH +PAPS O O NHC-CH 3 S OH O O + PAP NH 2 +PAPS NHSO 3 H +PAP LOGO Acylation 水杨酸与甘氨酸结合反应 COOH OH + H 2 NCH 2 COOH OH CO NHCH 2 COOH LOGO Acylation 磺胺类药物 A significant example is the acetyl metabolite of some of the sulfonamides. Some of the sulfonamides are acetylated to relatively insoluble metabolites which precipitated in urine, crystalluria NH 2 SO 2 NHR + Co-S-C-CH O SO 2 NHR NHC-CH 3 + CoA-SH O LOGO methylation 结合部位发生在药物结构的N、O、S等杂原子 烟酰胺→N-甲基烟酰胺 less polarity N CONH 2 CONH 2 N + CH 3 LOGO 新生儿及幼儿的氯霉素代谢 4-5岁幼儿 t1/2=4h 10-15d t1/2=10h 1-2d t1/2=27h LOGO 安替比林 * * * * * * * * * * * * * * * LOGO (三）肝清除率（Hepatic clearance,CLH ) 定义：指单位时间内有多少体积血浆中所含的药物被肝脏清除掉。 = Q(Cin-Cout) Cin CLH = C dX dt = Q×ER The volume of plasma w