IND申请的DMPK实验设计与时间安排-实例分析与探讨.pdf

Confidential information IND申请的DMPK实验设计与时间安排  IND 需要哪些DMPK实验- What ？ - 最少需要哪些实验？  实验设计– How？ -具体实验设计 -DMPK实验与药效及毒性试验有什么关系？ -已经在筛选阶段完成部分DMPK实验，是否重复？  IND申请的DMPK实验的时间安排– When ？ -什么时候开始？ -各项DMPK实验的先后顺序？ -DMPK实验与药效及毒性试验后顺序？ Confidential information 2 IND 需要哪些DMPK实验- What ？ - 最少需要哪些实验？ 答案： 没最少，要更好! Confidential information 3 IND申请的DMPK实验内容 2.6.4 Pharmacokinetics Written Summary Table of Contents  ADME • Absorption, distribution, 1. Brief Summary 2 metabolism, and excretion 2. Methods of Analysis4 3. Absorption 5 3.1 Rat Pharmacokinetic Study 5 3.2 Dog Pharmacokinetic Study 6 3.3 Caco-2 Monolayer permeability assay 7 • Information is collected 4. Distribution9 over the entire course of 4.1 Tissue distribution 9 4.2 Blood /plasma ratio 10 development – At the IND 4.3 Plasma Protein Binding 10 filing stage, you should be 5. Metabolism 12 starting to get an 5.1 Metabolic stability and Metabolite identification 12 5.2 CYP inhibition 14 understanding on the 5.3 Phenotyping 15 ADME basics of your drug 5.4 CYP induction 15 6. Excretion 17 7. Discussion and Conclusions 17 8. References 18 Confidential information 4 Absorption Absorption Type of Study