Correlation of Clinical Response with Drug
Disposition
Submitted by: Asad Nosheerwan
Submitted to: Dr. Atif Usman
Pharmacokinetic and Pharmacodynamics Correlation
The clinical response depends on the concentration of the drug at the target site, but
since this is difficult to measure directly, plasma concentration is used as a surrogate to
design dosage regimens that achieve therapeutic effects while minimizing side effects.
• Pharmacokinetic Data: Provides insight into how much drug is available in the
bloodstream and how long it stays there.
• Pharmacodynamics Response: Produces due to relation between plasma
concentration and the effect it produces on the body (e.g., therapeutic or adverse
effects).
Models for Understanding Pharmacokinetic-
Pharmacodynamic Correlation
1. Pharmacodynamics-Pharmacokinetic Models at Steady State: Focuses on
the relationship between drug concentration and clinical response when drug
levels are constant.
2. Pharmacodynamic-Pharmacokinetic Models: Explores the dynamic
relationship between changing drug concentrations and clinical responses over
time.
3. Physiologic-Pharmacokinetic Models: Incorporates physiological factors (e.g.,
organ function) to predict how a drug is distributed and metabolized in the body,
influencing its pharmacodynamics.
Pharmacodynamics-Pharmacokinetic Models at
Steady State
A pharmacokinetic model at steady state describes the behaviour of drug concentration
in the body when the rate of drug administration equals the rate of elimination. Drug
levels fluctuates between a minimum (trough) and maximum (peak) with multiple
dosing. Steady state is usually reached after 4-5 half-lives of the drug.
Types of Models:
• Fixed Effect Model
• Linear Model
• Log Linear Model
• Non Linear Model
1. Fixed Effect Model
2. Linear Model
3. Log-Linear Model
4. Nonlinear Model
2. Pharmacodynamics-Pharmacokinetic Model
1. Direct Effect Model
• It is used when the drug works quickly after it reaches the blood.
• The effect changes as the drug concentration in the blood changes.
• Example: A painkiller that reduces pain as soon as the drug level rises.
Common Equation:
E = Emax · C / EC50 + C
• E = effect
• Emax = maximum possible effect
• C = drug concentration
• EC50 = concentration that gives 50% of the max effect
2. Effect Compartment (Link) Model
• It is used when there is a delay between drug concentration and its effect.
• A "virtual" compartment is added to represent the delay before the drug shows its
effect.
• Example: Sleeping pills that take 30 minutes to make you sleepy after reaching
your blood stream. (Zolpidem → Temazepam)
3. Indirect Response Model
• It is used when the drug doesn’t act directly, but affects something the body
makes or breaks down.
• The drug may increase or decrease the production of something (like a
hormone), or increase or decrease its removal.
• Example: A drug that reduces inflammation by blocking the production of
inflammatory chemicals.
3. Physiological-Pharmacokinetic Model
• Describes effects mediated by indirect mechanisms, separate from the true drug
action site.
• Used to link plasma drug concentration to physiological process changes.
• Example: Warfarin anticoagulant effect predicted via prothrombin time.
In Vitro Response Models
• Combine in vitro and in vivo data to predict concentration-effect relationships.
• Often used in drug development and regulatory science.
• Not yet fully validated but valuable for early-stage predictions.
• Used to simplify PK-PD correlation.
Various software used in this study: Origin Lab, Phoenix WinNonlin, Dotmatics, etc.
Thank you for your attention!