FDA Drug Approval Process

2. FDA Drug Approval Process

5. Pharmacokinetics

7. Therapeutic Window

8. Pharmacodynamics Effect of treatment

9. Graded response saturates and may be described by C is what comes from the PK analysis hence one then knows the treatment response from equation at left

10. Drug Entry

12. 1. Prefer plasma drug concentration since it is quicker and not interfered by hemolysis and release of RBC proteins 2. Drug concentration as measured is usually the total plasma concentration or what is known as the unbound and bound drug concentration 3. Drug effect, distribution, and elimination is due to unbound drug concentration 4. fu is the fraction unbound = Cu/Ctotal and is usually constant so either Cu or Ctotal can be used in a PK analysis, just be sure to know what you are using

13. Splanchnic circulation takes the drug from the GI tract directly to the liver for what is called first pass elimination, which can significantly reduce the amount of drug that is available for a given dose.

15. Diffusion through the lipid bilayer depends on the solubility of the drug. Environment is aqueous, lipid, then aqueous in the cell Standard way of describing the lipid solubility of a drug is by the logP Which is also the octanal/water partition coefficient which is defined as: logP > 0 means the drug is more soluble in octanal than in water and are therefore called lipophilic drugs logP < 0 means the drug is less soluble in octanol than in water and are more hydrophilic Optimal logP for passive diffusion across the lipd bilayer of cells is around 2-3

16. Increasing lipophilicity

18. Passive transport: rate = P S  C Carrier mediated Transport: Note only the unbound drug is transported, bound drug is usually with albumin which is too big

20. Perfusion limited - Tissue membranes present no resistance to drug transport Permeability limited – membranes of the capillaries and cells limit transport

21. Perfusion rate limited Permeability- limited

22. Permeability rate limited