Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Outline of presentation
3. Central nervous system diseases
4. Drug market for CNS disorders
5. Traditional CNS drug targets
6. Novel CNS drug targets
7. Multiple obstacles for drug delivery to CNS
8. Pathways for drug exchange within the CNS
9. Factors affecting brain drug delivery and exchange
10. The structure of brain capillaries impedes uptake
11. Measures of drug uptake and distribution in brain
12. BBB permeability and solute lipid solubility
13. Tissues capillary PS and 95% equilibration time
14. Cerebral blood flow affects drug uptake and Kin
15. Initial uptake vs. steady-state distribution
16. Plasma protein binding and brain drug uptake
17. Example of the impact of plasma protein binding
18. Brain capillary drug transporters
19. Transporters and drug distribution across BBB
20. "Enzymatic" blood-brain barrier
21. Drug distribution in brain at steady state
22. Relation between bound and free drug
23. Free drug distribution ratio at steady state
24. BBB changes in pathology and disease
25. Drug-like properties to cross the BBB
26. Early findings in BBB drug uptake
27. Measures of lipophilicity
28. Passive permeability across lipid membranes
29. Drug ionization
30. Influence of pH on neutral fraction
31. Lipinski "rule of five"
32. "Rule of five" modified for CNS drugs
33. Impact of hydrogen bonds and alkyl groups
34. Examples of positive CNS drugs
35. Example of a poor CNS drug
36. Other in vitro measures
37. In vivo measures
38. Methods to improve brain uptake
39. Simple rules for efflux transporters
40. % drug distribution to brain
41. Biologic compounds
42. Closing comments of brain pharmacokinetics
43. Summary
44. Acknowledgements

Topics Covered

• Central nervous system diseases
• Drug market for CNS disorders
• Traditional CNS drug targets
• Novel CNS drug targets
• Multiple obstacles for drug delivery to CNS
• Pathways for drug exchange within the CNS
• The structure of brain capillaries impedes uptake
• Measures of drug uptake and distribution in brain
• BBB permeability and solute lipid solubility
• Tissues capillary PS and 95% equilibration time
• Cerebral blood flow affects drug uptake and Kin
• Initial uptake vs. steady-state distribution
• Plasma protein binding and brain drug uptake
• Brain capillary drug transporters
• Transporters and drug distribution across BBB
• "Enzymatic" blood-brain barrier
• Relation between bound and free drug
• Free drug distribution ratio at steady state
• BBB changes in pathology and disease
• Drug-like properties to cross the BBB
• Early findings in BBB drug uptake
• Measures of lipophilicity
• Passive permeability across lipid membranes
• Drug ionization
• Influence of pH on neutral fraction
• Lipinski "rule of five"
• Impact of hydrogen bonds and alkyl groups
• Positive CNS drugs
• Poor CNS drug
• in vitro measures
• In vivo measures
• Methods to improve brain uptake
• Simple rules for efflux transporters
• % drug distribution to brain
• Biologic compounds
• Brain pharmacokinetics

Links

Series:

• The Blood-Brain Barrier
• Small Molecule Drug Discovery

Categories:

• Neuroscience
• Pharmaceutical Sciences

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on March 1, 2008
• Archived on May 31, 2018

Financial Disclosures

• Prof. Quentin Smith has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.