TOPIC : PHARMACOKINETIC MODELS

PREPARED BY
MD. ASADUZZAMAN
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACY
CONTACT: 01712148888
What is a Pharmacokinetic Model
► A Pharmacokinetic model is a hypothesis using
mathematical terms to describe quantitative
relationships concisely.
► Such mathematical models can be devised to simulate
the rate processes of drug absorption, distribution, and
elimination(ADME) to describe and predict drug
concentrations in the body as a function of time.
Usefulness/Importance of PK models
Pharmacokinetic models are used to:
1. Predict plasma, tissue, and urine drug levels with any
dosage regimen
2. Calculate the optimum dosage regimen for each patient
individually
3. Estimate the possible accumulation of drugs and/or
metabolites
4. Correlate drug concentrations with pharmacologic or
toxicologic activity
Usefulness/Importance of PK models
5. Evaluate differences in the rate or extent of availability
between formulations (bioequivalence)
6. Describe how changes in physiology or disease affect the
absorption, distribution, or elimination of the drug
7. Explain drug interactions
(Ref: pg-15 /Shargel)
Types of PK Models

Three types of PK models could be described-

1. Empirical Models (Non-compartmental Analysis)
2. Physiological Models
3. Compartment Models

(Ref: pg-16 /Shargel)

1.Empirical Models (Non compartmental
Analysis)
o The model that simply interpolates the data and allows
an empirical formula to estimate drug level over time is
justified when limited information is available.
o Empirical models are practical but not very useful in
explaining the mechanism of the actual process by which
the drug is absorbed, distributed, and eliminated in the
body.
Ref: pg-16 (Shargel)
1.Empirical Models (Non compartmental
Analysis)

Noncompartmental analyses are based on statistical

moment theory, which provides a unique way to study
time-related changes in macroscopic events. For
example, We can use this model to calculate Mean
Residence Time (MRT) of a drug.
Ref: pg-836 (Shargel)
Mean Residence Time (MRT)
The term MRT describes the average time that drug
molecules stay in the body or in a kinetic space.
The equation to calculate the MRT following intravenous bolus or
constant infusion administrations is described by following equation-
MRT= (AUMC/AUC) - Duration/2

Ref: pg-837 (Shargel)

Mean Residence Time (MRT)
► Graphical presentation of AUC and AUMC
Non compartmental Analysis
Advantages….
1. Ease of derivation of pharmacokinetic parameters by simple algebraic
equations.
2. The same mathematical treatment can be applied to almost any drug
or metabolite provided they follow first order kinetics.
3. A detailed description of drug disposition characteristics is not
required.
Disadvantage…..
This method provides limited information regarding plasma drug
concentration-time profile; more often, it deals with averages.
Ref: pg-225( Brahmankar)
2. Physiologic Model
► Physiological pharmacokinetic models are
mathematical models describing drug movement and
disposition in the body based on organ blood flow and
the organ spaces penetrated by the drug.
► In its simplest form, a physiologic pharmacokinetic
model considers the drug to be blood flow limited.
Drugs are carried to organs by arterial blood and leave
organs by venous blood. Ref: pg-828 & 830 (Shargel)
2. Physiologic Model
2. Physiologic Model
Advantages….
1. The model gives exact description of drug conc.-time profile in
any organ and tissue and thus better picture of drug
distribution characteristics in the body.
2. Drug conc. can be predicted on the basis of organ or tissue
volume, perfusion rate and experimentally determined tissue
to plasma partition co-efficient.
3. The influence of altered physiology or pathology on drug
disposition can be easily predicted.
2. Physiologic Model
Advantages….
4. Mathematical treatment is straight forward.
5. Correlation of data in several animal species is possible and
with some drugs, can be extrapolated to human.
Disadvantage……
The only disadvantage of these models is obtaining
experimental data which is very exhaustive.
Ref: pg-227 (Brahmankar)
Refereces

✔ Applied Biopharmaceutics and Pharmacokinetics – Leon Shargel

and Andrew Yu; 7th edition.
Chapter-1, Pg: 15,16; Chapter-25, pg- 828,830, 836,837.
✔ Biopharmaceutics and pharmacokinetics- D.M.Brahmankar and
Sunil B. Jaiswal
Chapter-9, Pg: 220-227
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