1. ADME
And
PHARMACOKINETICS

2. ADME lecture 1 Contents ... What are ADME and Pharmacokinetics?
Absorption
Distribution

3. What are ADME and pharmacokinetics?
Part 1
What are ADME and pharmacokinetics?

4. PHARMACOKINETICS “Drug movement” (Greek)
Mathematical description of the
various processes that constitute
ADME.

5. ADME
Absorption
Distribution
Metabolism
Excretion
Elimination

6. Absorption The movement of drugs into the body
Do not consider a drug to be fully absorbed until it reaches the blood stream. Drugs administered orally, intramuscularly, subcutaneously etc need to undergo absorption (unless effect is to be topical).
Only i.v. route does not require absorption.

7. Distribution The movement of drugs around the body
Once absorbed, drugs will generally move around the body. A drug molecule may spend some time in one organ, then be carried by the blood to another organ and so on …

8. Elimination The removal of drugs from the body
Elimination is the final removal of the drug from the body. This is subdivided into…
Metabolism: Destruction of the drug by chemical alteration.
Excretion: Removal of the drug from the body (Generally in the urine). Note that the term ‘Excretion’ is only used if the drug is removed chemically unaltered.

9. Part 2
Absorption

10. Absorption Three mechanisms by which drugs may cross membranes:
Passive diffusion
Facilitated diffusion
Active transport
Passive diffusion MUCH more common than any of the others.

11. Passive diffusion
Lipid
Water
DRUG

12. Requirements for passive diffusion
Water solubility
Lipid solubility
Almost all drugs are sufficiently water soluble to undergo passive diffusion, but some do lack the necessary lipid solubility.
In practice, passive diffusion depends mainly on lipid solubility.

13. Specificity of passive diffusion
Non-specific.
No requirements as to the
size or shape of the molecule, just so long
as it is lipid soluble.

14. Efficiency of passive diffusion

15. Facilitated diffusion and active transport
Both operate via a transport protein that carries a molecule across a membrane.
Active transport is energy requiring, but facilitated diffusion is not.
The transport proteins will only carry structurally specific groups of molecules e.g. amino acids
Very few drugs have structures sufficiently similar to any naturally occurring group of molecules that have a carrier protein. Therefore rarely arises.

16. Part 3
Distribution

17. Distribution
Kidneys
Fat
Blood
etc
Liver

18. Factors influencing distribution of a drug:
Ability to undergo passive diffusion (Already described)
Binding to macromolecules

19. Plasma protein binding
BLOOD
CELL
Drug
Drug
Drug.Protein
Lipid
Total drug concentration in blood greater than in cell.

20. Intra-cellular binding
BLOOD
CELL
Drug
Drug
Drug.Protein
Lipid
Nucleic acid
Lipid
Total drug concentration in blood lower than in cell.

21. Overall binding BLOOD CELL Drug Drug Drug.Protein Drug.Protein Lipid
Nucleic acid
Lipid
Balance depends upon relative binding affinity in blood and tissues.

22. Terms with which you should be familiar ...
ADME Pharmacokinetics
Absorption Passive diffusion
Distribution Faciliated diffusion
Metabolism Active transport
Excretion
Elimination

23. What you should be able to do
Distinguish between metabolism and excretion
Describe the mechanism of passive diffusion
Predict whether a given molecule will easily undergo passive diffusion
Identify the factors that may influence the distribution of a given drug