Lecture 1
INTRODUCTION TO
PHARMACOKINETICS
Leon Aarons
Manchester Pharmacy School
University of Manchester
OBJECTIVES
The participant will be able to:
1. List applications of pharmacokinetics
2. Define the terms: absorption, disposition,
distribution, elimination, excretion,
metabolism
3. Describe various models used to
characterise the kinetics of absorption and
disposition
4. Describe the role of pharmacokinetics in
drug development
PHARMACOKINETICS (PK)
Figure 1 The relationship between drug administration and response can
be divided into pharmacokinetics and pharmacodynamics.
Pharmacokinetics(PK): How body handles drug
Pharmacokinetics(PK): How
handles drug
Pharmacodynamics(PD): What drug does body
to body
Pharmacodynamics(PD): What drug does to body
PK Processes - ADME
Disposition
Distribution Elimination
Absorption
Metabolism
Blood +
Excretion
Figure 2
All defined with respect to site of
measurement, usually drug in blood or
plasma in vivo
PK PROCESES
1. Absorption -
All processes from site of administration to site of measurement.
Bioavailability - defined here as a measure of the extent of
absorption of unchanged administered compound.
2. Distribution -
Reversible transfer of substance between site of measurement and
other sites within the body.
3. Metabolism -
Irreversible loss of unchanged substance by chemical conversion.
4. Excretion -
Irreversible loss of unchanged substance
5. Elimination -
Irreversible loss of unchanged substance from site of measurement
6. Disposition -
Elimination and distribution
PK
d
PROCESES
Fig 3 shows -
• Major organs of
the body
• Sites of drug
absorption (*a –
e), distribution
and elimination
APPLICATIONS OF
PHARMACOKINETICS
1. Relates temporal patterns of response
(efficacy, toxicity) to drug administration
following acute and chronic dosing
2. Helps provide a rational basis for drug design,
drug selection and dosage regimen design
3. Helps evaluate quantitatively drug product
performance in vivo (bioavailability), and
establish appropriate in vitro dissolution
specifications
4. Provides a means for comparing data from
different animal species
Quantitative framework for drug
design, evaluation and
administration
1. PK behaviour is a function of –
Physicochemical & structural
properties of drug
Dosage form
Route of administration
Physiology/anatomy of the body
2. Poor pharmacokinetic properties of a
drug may limit its clinical application
Quantitative framework for drug
design, evaluation and
administration - 2
3. Factors influencing the
pharmacokinetics of a drug include
genetics, size, age, disease, other
drugs, environmental factors
4. Components of pharmacokinetics -
data (primary e.g. concentration, or
derived e.g. cumulative amount
excreted) and models.
Need to relate pharmacokinetics to
pharmacodynamics (PK/PD)
MODELS FOR DRUG ABSORPTION
AND DISPOSITION
Sometimes sufficient to define events in terms
of observations, such as maximum
concentration (Cmax) and time to achieve it (tmax)
after oral administration
Many times, however, a model is required to:
• summarize the data
• permit interpolation
• facilitate extrapolation and prediction.
• facilitate understanding
Generally, the more mechanistic the model the
greater the ability to make predictions
Choice of models
1. Equations e.g. C a e bt
2. Physiologic Models (see also Figure 2)
Figure
Figure 84
Note: A major tool in prediction of in vivo pharmacokinetics from in vitro data.
3. Kinetic Compartmental Models
Number of compartments defined by the data
Kinetic compartment
models
b. Two-compartment model
a. One-compartment (body) model
Figure 5 Figure 6
Simple compartment model of
drug absorption and
elimination
Figure 7
Amount at Amount Amount Amount
Dose (1)
absorption site in body excreted metabolised
Rate of change Rate of Rate of Rate of
excretion (2)
of drug in body absorption metabolism
Rate of change Rate of Rate of Rate of
excretion (2)
of drug in body absorption metabolism
Figure 8
PHARMACOKINETICS AND
DRUG DEVELOPMENT