Relationship Between
Pharmacokinetics and Pharmacodynamics-
PKPD Model
By
Kh. Hussan Reza
[Link], (Ph.d)
What is Pharmacokinetics (pk) and Pharmacodynamics(PD) &
their relationship?
Pharmacokinetics ---- drug disposition process -----
determines drug exposure in the body----- correlated to desirable
(Efficacy) and undesirable (toxicity)---
Pharmacodynamics(availability of drug for receptors).
Pharmacokinetics expressed mathematically –
compartmental, noncompartmental models.
Pharmacokinetics( dose regimen, concentration, dose)
correlated with the effect (Pharmacodynamics)–
Mathematical model – PK-PD Model
Terminologies have been used to describe PK and PD:
1. Exposure
The term exposure can be defined as any dose or drug input to the
body or various measures of acute or integrated drug concentrate-
in plasma or other biological fluid (eg, Cmax, Cmin, Css, AUC, Cp), relates to the
amount at site of effect.
2. Response
A response (R) refers to a direct measure of the pharmacologic observation. For
example, measure of diastolic blood pressure (DBP) at some time point is
considered as a response.
R(t) = Response at time, t : Diastolic blood pressure.
3 types Response
a. Continuous: blood glucose levels, blood pressure readings, or enzyme levels.
b. Categorical: death or no death, graded pain score, number of seizures in a month.
c. Time to event outcomes: time to relapse , time until transplant
3. Effect
The effect, E refers to a change in the biological response from one
time to another. In other words, an effect is a derived or calculated
value from an observed response. For example, a change from
baseline in diastolic blood pressure is the effect.
E = Effect : Change from baseline in DBP at 8 weeks ; R(0)=
92mmHg, R(8)= 82mmHg , E= R(8)-R(0)= 92-82=10 mmof Hg.
PK-PD Information Flow in drug development:
PK-PD Model :The Concept
The pioneering work of Gerhard Levy in the mid-1960s
Characterizes the PK of a drug, relates PK to the PD (EXPOSURE
& RESPONSE), and is then applied for predictions of the response
under new conditions- EFFECT (eg, new dose or dosing regimen).
PK model or function: PD model or function:
Theta-PK :Clearance (Cl), Theta –PD:maximum effect,
and volume of distribution Emax and potency of the
(VD). drug, EC50.
X : dose, dosing regimen, Cp or Ce are the
t is the time. concentrations of the drug
Ce: effect site referred to as in plasma or at the biophase
bio-phase concentrations, Ke0= between plasma and
Ce. the bio- phase.
kin and kout, which
formation (for influx) and
degradation (for efflux) rate
constants of the biosignal