1. MS WinNonLin Project
9/28/15: PK Modeling I project due today.

2. Time Delays between Concentration and Response
Lecture #17
Time Delays between Concentration and Response

3. Pharmacodynamics vs. Pharmacokinetics
Pharmacodynamics (PD)
What the drug does to the body?
Pharmacokinetics (PK)
What the body does to the drug?
ADME

4. Pharmacodynamics [Drug]Site of ActionResponse or Effect
Response (E)
Therapeutic
Adverse Drug
Reaction (ADR)

5. PD Terms to Know Minimum Effective Dose (MED) and Concentration (MEC)
Maximum Tolerated Dose (MTD) and Concentration (MTC)
Effective Dose (ED)
ED50 (50% of the population)
ED95 (95% of the population)
[Drug]
ADR

6. Time Delay

7. Time Delay

8. Time Delay and Hysteresis

9. Time Delay and No Hysteresis

10. Time Delay and Hysteresis

11. Time Delay Causes Slow Distribution Metabolism Active Metabolite
Pharmacodynamics

12. Causes of Hysteresis Counter-clockwise Clockwise time time
Counter-clockwise hysteresis
1) Distribution Delay (Delay to get to target to induce response)2) Response Delay (Multiple step process)
3) Active Metabolite (Needs to be converted into an active metabolite first.)
4) Sensitization (Response increases with time)
Clockwise Hysteresis
1) Tolerance
Potential Causes
Distribution Delay
Response Delay
Active metabolite
Sensitization
Potential Causes
Tolerance

13. Cocaine and Tolerance
Cocaine
Other examples: Capsaicin

14. Ibuprofen and Pharmacodynamics

15. Pharmacodynamics

16. Pharmacodynamics

17. Pharmacodynamics

18. System in Flux
e.g. Protein
Synthesis
e.g. Protein
Degradation

19. Systems in Flux

20. System in Flux
Prothrombin
Thrombin

21. Systems in Flux
What is dclot/dt equal to at steady state?

22. Systems in Flux
How do you figure out Rsyn?

23. Effect Compartment

24. Effect Compartment