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

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

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

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

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 http://image.slidesharecdn.com/tugasterjemahankirimkeahta2010gmail-140715235955-phpapp02/95/kimia-medisinaladme-3-638.jpg?cb=1405468892

Time Delay

Time Delay

Time Delay and Hysteresis

Time Delay and No Hysteresis

Time Delay and Hysteresis

Time Delay Causes Slow Distribution Metabolism Active Metabolite Pharmacodynamics

Causes of Hysteresis Counter-clockwise Clockwise time time http://www.australianprescriber.com/magazine/18/4/102/4/ 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

Cocaine and Tolerance Cocaine Other examples: Capsaicin

Ibuprofen and Pharmacodynamics http://en.wikipedia.org/wiki/Ibuprofen

Pharmacodynamics

Pharmacodynamics

Pharmacodynamics

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

Systems in Flux

System in Flux Prothrombin Thrombin

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

Systems in Flux How do you figure out Rsyn?

Effect Compartment

Effect Compartment