2. FDA Drug Approval Process

5. Pharmacokinetics

6. Upper therapeutic limit
Lower therapeutic limit
concentration

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

11. Table 8.1
Enteral routes mean the GI tract: buccal (mouth), sublingual
(under the tongue), gastric (stomach), intestinally (small & large), and rectally
Table 8.2

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,
see equation 8.1 in the book

13. Splanchnic circulation (viscera or entrails) 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 of the cell 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 octanol/water partition coefficient which is defined as:
logP > 0 means the drug is more soluble in octanol 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 lipid bilayer of cells is around
2-3

16. Increasing lipophilicity

18. For capillary Pm see Fig 6.5
of the book
Passive transport: rate = Pm S  C
Carrier mediated
Transport:
Here C is Ctotal and 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. Perfusion rate limited
Permeability rate
limited
Now we will discuss the Krogh tissue cylinder model section 6. and the
Renkin Crone model of section in the book
for finding the Pm of a solute across the capillary wall