新药临床评价
DESCRIPTION
新药临床评价. 阳国平 中南大学湘雅三医院临床药理中心. II 相代谢. II 相代谢. II 相代谢. 葡萄糖醛酸结合. P450. P450. 酯酶 水解. A. A. P450. B. P450. P450. P450. P450. 单羟基化. B. P450. 单羟基化. N- 氧化. 单羟基化. 单羟基化. Losartan 与 ALS-3 的代谢途径比较图. 2001 年在全球药品销售额排序第十位. 特非那丁. 非索非那定. 3A4. 阻断心肌慢钾离子 通道受体. 康唑类 大环内酯类. 抗 H 1. - PowerPoint PPT PresentationTRANSCRIPT
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LosartanALS-3N-P450AP450A P450BP450P450P450P450IIIIBP450II
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P450 3A4H1Torsades
pointes1998FDA
19861996WHO1797698 De 2001
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colestimideCarmoxirole Fantofarone Rufinamide NXY059CeroviveAGM1470 PEGABI007Ferumoxtran-10.
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2007101
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CMC:
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161747520James Lindt 19481951Robert Austrian
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whathowwhy
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1.123456
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4.5.6.
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I
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ICH-E6 GCPE7 E8 E9 E10 E11E12AE14QT/QTc
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ICH-E6 GCPE7 E8 E9 E10 E11E12AE14QT/QTc
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20-40 16-8 2-4 6-8 1
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Blach well LD501/600 1/60Blach well () LD501/600 1/60 Dollry ( 1/50-1/100Fibonacci () LD101/100 1/40-1/30
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((1) ( Fibonacci ): ,+1/3, +100%, +67%, +50%, +30%+35%, +1/3 I ---------------------------------------------------- 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3.3 5 6.7 9 12 16 21 28 38 50 1/1 1 2 4 8 16 32 64 128 1/2 1 1.5 2.2 3.4 5 7.6 11 17 26 38 58 87 1/3 1 1.3 1.8 2.4 3.2 4 5.6 7.5 10 13 18 24 ----------------------------------------------------(2) +1/1,+1/3,+1/2
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212-166-85-10
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GCP200391Good Clinical Practice, GCP)
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30-60P450EXP3174EXP3174AT1AT110~40AT1EXP3174EXP3174 Boris Schmidt [1]1ABAP450EXP3179EXP3174EXP31747[2]II BP450