INTRODUCTION TO

PHARMACOKINETICS &
PHARMACODYNAMICS

Dr Sindwa Kanyimba
Lecturer, Pharmacology
INTRODUCTION

• Pharmacokinetics refers to the movement of the drug

into the body, through the body, and out of the body; and
takes into account the processes of drug input
(absorption), drug distribution and elimination of the
drug from the body (metabolism and excretion)
• Pharmacodynamics describes the effects of drugs and
the mechanisms by which drugs exert their effects
LEARNING OBJECTIVES

• Explain the terms Pharmacokinetics and

Pharmacodynamics
• Explain the importance of pharmacokinetics and
pharmacodynamics in the determination of drug dosage
regimens
• Outline the four pharmacokinetic processes of Absorption,
Distribution, Metabolism and Excretion
• Differentiate between drug actions and drug effects
• Outline the mechanisms by which drugs produce their
effects
LEARNING OBJECTIVES …. CONT’D

• Describe the relationship between pharmacokinetics and

pharmacodynamics
• Describe the time course of drug action
• Describe the relationship between drug dose and clinical
response
• Define the terms Therapeutic Range and Therapeutic
Index
• Calculate the Therapeutic Index
PHARMACOKINETICS

Pharmacokinetics is the study of the processes involved in

the disposition of drugs, namely absorption, distribution,
metabolism and excretion (ADME), including:
• The rate and extent to which drugs are absorbed into
the body and distributed to the body tissues
• The rate and pathways by which drugs are eliminated
from the body by metabolism and excretion
• The relationship between time and plasma drug
concentration
PHARMACOKINETICS …. CONT’D

Understanding the pharmacokinetic processes is important

because:
• They form the basis on which the optimal dose regimen is
chosen
• They explain the majority of the inter-individual
variation in the response to drug therapy
PHARMACOKINETICS: ADME

Absorption
The process by which drugs enter the body
 Given by any route other than intravenously, drug
molecules must cross tissue membranes (e.g. skin
epithelium, subcutaneous tissue, gut endothelium,
capillary wall) to enter the blood
Distribution
The process by which drugs move around the body
 After entering the blood, drug molecules must cross
capillary walls to enter the tissues, reach cell membranes
and enter cells
PHARMACOKINETICS: ADME …. CONT’D

Metabolism
The process by which drugs are chemically altered to make
them sufficiently water-soluble for excretion in urine or
faeces (via the biliary tract)
 Metabolism occurs in a variety of body organs and
tissues, but chiefly in the liver, gut wall, kidney and skin
PHARMACOKINETICS: ADME …. CONT’D

Excretion
The process by which drugs leave the body
 Drugs that are sufficiently water-soluble will be
excreted unchanged in the urine
 Lipid-soluble drugs must be modified to water-soluble
metabolites before excretion via the kidney or into the
intestine via the bile
PHARMACOKINETICS: APPLICATION

• For a drug to produce a beneficial effect without

intolerable unwanted effects, it needs to be present in the
right place, at the right concentration and for the right
duration
• Changes in drug tissue and plasma concentration over
time is determined by the pharmacokinetic profile of the
drug
• Knowledge of drug pharmacokinetics is therefore
required for rational dosing; dose regimens are
determined from drug pharmacokinetic parameters
PHARMACODYNAMICS

Pharmacodynamics is the study of the biochemical and

physiological effects of drugs and their mechanisms of action
• Involves the study of the actions and effects of drugs
• Involves the study of the interactions between drugs and
cellular macromolecular components which result in
biological effects
DRUG ACTION VERSUS DRUG EFFECT

Drug action
Mechanisms by which the drug produces a response in
living organisms
Drug effect
The observable consequence of a drug action
 Example: The action of penicillin is to interfere with cell
wall synthesis in bacteria and the effect is the death of
the bacteria
MECHANISM OF ACTION VERSUS MODE OF
ACTION
Mechanism of action: Refers to the specific biochemical
interaction through which a drug produces its pharmacological
effect (= Drug Action)
Mode of action: Describes a functional or anatomical
change, resulting from the exposure of a living organism to a
drug (= Drug Effect)
Mechanism of action describe changes at molecular level
while mode of action describes changes at cellular level
MECHANISMS OF ACTION

Most drugs act by interacting with macromolecular targets

(mostly proteins) which include receptors, enzymes,
carriers, membrane bound transport proteins and pumps,
and ion channels
 Drugs action may lead to stimulation or depression of
normal physiological functions. Stimulation increases the
rate of activity while depression reduces the rate of
activity.
 Drugs may act by increasing or decreasing enzymes,
hormones or other chemical mediators of biological
activities

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RELATIONSHIP BETWEEN PHARMACOKINETICS
AND PHARMACODYNAMICS
RELATIONSHIP BETWEEN PHARMACOKINETICS
AND PHARMACODYNAMICS …. CONT’D
RELATIONSHIP BETWEEN PHARMACOKINETICS
AND PHARMACODYNAMICS …. CONT’D

• The pharmacokinetic properties of a drug determine the

concentration of drug achieved in plasma and tissues,
including the site of action of the drug
• Drug effects are proportional to the concentration of drug
at the action site
• An equilibrium is established between plasma drug
concentration and concentration at the active site,
therefore there is a correlation between drug effects and
plasma drug concentration
RELATIONSHIP BETWEEN PHARMACOKINETICS
AND PHARMACODYNAMICS

• Pharmacokinetics determines the change in plasma

drug concentration with time, and therefore how
rapidly and for how long the drug will appear at the
target organ
• Pharmacodynamics determines the magnitude of
drug effect in relation to plasma drug
concentration
RELATIONSHIP BETWEEN PHARMACOKINETICS
AND PHARMACODYNAMICS …. CONT’D

• The relationship between dose and effect can be

separated into two components:
1. Pharmacokinetic (dose-concentration)
2. Pharmacodynamic (concentration-effect)
• Plasma drug concentration forms the link between
drug dosing and drug effect
Dose → CONC → Effect
• Plasma drug concentration provides the link between
pharmacokinetics and pharmacodynamics and is
therefore the focus when determining a dose regimen
TIME COURSE OF DRUG ACTION

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TIME COURSE OF DRUG ACTION …. CONT’D

Onset of drug action

The time it takes after the drug is administered to reach a
concentration that produces a response
Duration of action
The time during which the drug is present in a concentration
large enough to produce a response
Peak effect
The time it takes for the drug to reach its highest effective
action

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TIME COURSE OF DRUG ACTION …. CONT’D

Onset of drug action

The time it takes after the drug is administered to reach a
concentration that produces a response
Duration of action
The time during which the drug is present in a concentration
large enough to produce a response
Peak effect
The time it takes for the drug to reach its highest effective
action

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RELATIONSHIP BETWEEN DRUG DOSE &
CLINICAL RESPONSE

Minimum effective dose (MED): The lowest dose level

of a drug that provides a clinically significant response
• There is a threshold for each drug to produce a response
• Doses of drugs below that threshold will produce no
observable effect
Maximum tolerated dose (MTD): The highest dose of a
drug that will produce the desired effect without
unacceptable toxicity

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RELATION BETWEEN DRUG DOSE & CLINICAL
RESPONSE …. CONT’D

100
Therapeutic
Toxic
80

% Responding 60

40

20
ED99
TD1 TD50
0 ED50
70 80 90100 200 300

Dose
RELATIONSHIP BETWEEN DRUG DOSE &
CLINICAL RESPONSE …. CONT’D

Median effective dose (ED50): The dose of a drug that

produces a specified effect in 50% of the population that takes
that dose
Median toxic dose (TD50): The dose of a drug that produces
a particular toxic effect in 50% of the population that takes
that dose
Median lethal dose (LD50): The dose of a drug required to
kill 50% of a given test population

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THERAPEUTIC RANGE (WINDOW) AND
THERAPEUTIC INDEX
Therapeutic range (therapeutic window)

The concentration of drug between minimum effective

concentration and maximum safe concentration is known as
therapeutic range

Range of the dose levels from the MED to the MTD

Therapeutic index

• MTD/MED

• TD50/ED50

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THERAPEUTIC RANGE (WINDOW) AND
THERAPEUTIC INDEX …. CONT’D

• The relative safety of a drug can be expressed by its

therapeutic index
• A drug with a wide therapeutic index has a high safety
margin and is relatively safe; the lethal dose is much
larger than the therapeutic dose
• A drug with a narrow therapeutic index is more dangerous
for the patient because small increases over normal doses
may induce toxic reactions

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 END
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