University of Gharyan

Faculty of Pharmacy

Pharmacokinetics and Pharmacodynamics of drugs

Ahmed Haider
1920-7002
Pharmaceutics II
Dr. Mawada Suliman
2023/5/19
 Pharmacokinetics and Pharmacodynamics of Drugs

Pharmacokinetics and pharmacodynamics are two fundamental concepts in

pharmacology that describe how drugs are absorbed, distributed, metabolized,
and excreted by the body, as well as how they interact with their target
receptors or enzymes to produce therapeutic or adverse effects.
A simple and useful distinction is to think of pharmacodynamics as “what
the drug does to the body” whereas pharmacokinetics is “what the body
does to the drug.” (1)

Pharmacokinetics

Pharmacokinetics refers to the study of how drugs move through the body,
including their absorption, distribution, metabolism, and excretion. These
processes are influenced by a variety of factors, including the properties of the
drug itself, patient-specific characteristics (such as age, sex, and genetic
background), and disease-related factors. The following sections will provide
an overview of each of these processes.
I) Absorption:
Drug absorption refers to the process by which a drug enters the bloodstream
from its site of administration. The rate and extent of absorption depend on
several factors, including:
• Route of administration: The route of administration affects the rate
and extent of drug absorption. Routes of administration can be divided
into two main categories: enteral and parenteral. Enteral routes of
administration include oral, sublingual, rectal, and nasal routes, while
parenteral routes of administration include intravenous, intramuscular,
subcutaneous, and inhalation routes. The route of administration affects
how quickly a drug enters the bloodstream and how much of the drug is
absorbed.
• Chemical properties of the drug: The chemical properties of the drug
can also affect drug absorption. Factors such as solubility, molecular
weight, and ionization can impact a drug's ability to cross cell membranes
and be absorbed into the bloodstream.
• Patient factors: Various patient factors can also affect drug absorption.
These include age, gender, body weight, and overall health. Patients with
certain medical conditions, such as gastrointestinal or liver disease, may
experience altered drug absorption.
• Food and drug interactions: Food and drug interactions can also affect
drug absorption. Some drugs may be absorbed more efficiently when
taken with food, while others may be absorbed less efficiently.
Additionally, certain foods or beverages may interact with drugs and
alter their absorption.
• Formulation factors: The formulation of a drug can also affect its
absorption. For example, the use of different excipients in a drug
formulation can affect its solubility and absorption. The presence of
coatings or sustained-release formulations can also affect the rate and
extent of drug absorption.
II) Distribution:
Following absorption, drugs are distributed throughout the body via the
bloodstream. The distribution of a drug depends on several factors, including
its physicochemical properties, the characteristics of the patient (such as body
weight and composition), and the presence of disease or other drugs that may
affect distribution.
In general, lipophilic drugs (i.e., drugs that are soluble in lipids) tend to
accumulate in fatty tissues, while hydrophilic drugs (i.e., drugs that are soluble
in water) tend to distribute more evenly throughout the body.

III) Metabolism:

Drug metabolism refers to the process by which drugs are biotransformed by

enzymes in the liver (the primary site for drug metabolism) and other tissues.
This process can result in the formation of metabolites that may be more or less
active than the parent drug.
A variety of factors may affect the activities of the enzymes involved in
metabolizing drugs. They are grouped into;
1. Chemical factors
• Enzyme induction
• Enzyme inhibition
• Environmental chemicals
2. Biological factors
• Age
• Diet
• Sex differences
• Species differences
• Strain differences
• Altered physiological factors
3. Physiochemical properties of the drug (2)
IV) Excretion

Drug excretion refers to the process by which drugs and their metabolites are
eliminated from the body, through renal or non-renal route.
Excretion, along with metabolism and tissue redistribution, is important in
determining both the duration of drug action and the rate of drug elimination.
Organs involved in excretion:

• Kidneys (Renal Excretion)

• Bile (Biliary Excretion)
• Lungs (Pulmonary Excretion)
• Saliva (Salivary Excretion)
• Breasts (Mammary Excretion)
• Sweat (Skin Excretion)

Pharmacokinetic variation
Pharmacokinetic variability results from differences between patients in the
absorption, distribution, elimination, and metabolism of a drug. Thus, a given
dose may produce different drug concentration profiles against time in
individual patients.
The most important factors in variability of pharmacokinetic parameters are:

1. Genetic
2. Disease
3. Age and body size
4. Concomitant drugs
5. Environmental factors (e.g., foods, pollutants)
6. Other factors include compliance, pregnancy, alcohol intake, seasonal
variations, gender, or conditions of drug intake. (3)
 Pharmacodynamics

Pharmacodynamics is the study of how drugs interact with the body and
produce their effects. It is a branch of pharmacology that examines the
relationship between the concentration of a drug at the site of action and the
magnitude of the resulting effect. This involves understanding how drugs bind
to specific receptors or other targets in the body, and how these interactions
lead to changes in cellular and physiological processes.
The following sections will provide an overview of the basic principles of
pharmacodynamics.
Mechanisms of Drug Action
The mechanisms by which drugs produce their effects can vary widely
depending on the specific drug and target receptor or enzyme.
There are several mechanisms by which drugs can produce their effects in the
body. These mechanisms can be broadly categorized into four main types:
receptor-mediated, enzyme-mediated, physicochemical, and genetic.
1. Receptor-mediated: Many drugs work by binding to specific receptors
on cells, such as neurotransmitter receptors, hormone receptors, or ion
channels. This binding can cause a range of effects, including activation
or inhibition of signaling pathways, changes in ion channel function, or
modulation of gene expression.
2. Enzyme-mediated: Some drugs function by inhibiting or activating
specific enzymes in the body. For example, many antibiotics work by
inhibiting bacterial enzymes that are essential for cell wall synthesis or
DNA replication.
3. Physicochemical: Some drugs produce their effects through
physicochemical interactions with cellular components. For example,
antacids work by neutralizing stomach acid, while osmotic laxatives
work by drawing water into the colon to increase stool volume.
4. Genetic: A growing number of drugs are being developed that work by
targeting specific genes or genetic pathways. For example, gene therapy
involves introducing new genetic material into cells to correct or replace
defective genes, while RNA-based therapies target RNA molecules to
modulate gene expression.
Types of Drug Effects
Drugs can produce a wide range of effects in the body, which can be classified
into several broad categories:
1. Therapeutic effects: These are the desired effects of a drug that lead to
the treatment or prevention of a specific medical condition. For example,
an antibiotic's therapeutic effect is to kill bacteria and cure an infection.
2. Adverse effects: These are unwanted or harmful effects of a drug that
can occur at therapeutic doses. Adverse effects can range from mild, such
as nausea or dizziness, to severe, such as liver damage or anaphylaxis.
3. Side effects: These are unintended effects of a drug that are not related
to the drug's primary therapeutic effect. They may be beneficial, neutral,
or harmful. For example, a medication that is used to treat high blood
pressure may also cause drowsiness as a side effect.
4. Tolerance: Tolerance occurs when the body adapts to the effects of a
drug, leading to a reduced response over time. This can require higher
doses of the drug to achieve the same effect.
5. Dependence: Dependence occurs when the body becomes physically or
psychologically reliant on a drug. Withdrawal symptoms may occur if the
drug is stopped abruptly.
6. Allergic reactions: Some people may have an allergic reaction to a drug,
which can range from mild symptoms such as hives or itching to severe
reactions such as anaphylaxis.

Dose-Response Relationships

The relationship between drug dose and drug effect can be described by a dose-
response curve, which illustrates the magnitude and variability of drug effects
at different doses. The shape of the dose-response curve can vary depending on
several factors, including the properties of the drug, the characteristics of the
patient, and the route of administration. The slope and position of the dose-
response curve can be influenced by factors such as drug potency, efficacy, and
toxicity.
The Therapeutic index

The therapeutic index (TI; also known as therapeutic ratio) is a ratio that
compares the blood concentration at which a drug becomes toxic and the
concentration at which the drug is effective.
This relationship is defined as the ratio LD50:ED50, where LD50 is the dose at
which a drug kills 50 percent of a test group of animals and ED50 is the dose at
which the desired effect is produced in 50 percent of a test group.
In general, the larger the therapeutic index, the safer the drug is. And the
smaller it is, the more likely it is that the drug will produce unwanted effects,
which in this case the drug must be dosed carefully and the person receiving
the drug should be monitored closely for any signs of drug toxicity.
The common method used to derive the TI is to use the 50% dose-response
points, including TD50 (toxic dose) and ED50 (effective dose).

For example, if the TD50 is 200 and the ED50 is 20 mg, the TI would be 10.

A clinician would consider a drug safer if it had a TI of 10 than if it had a TI of 3.

However, the therapeutic index has many limitations, notably the fact that
LD50 cannot be measured in humans and, when measured in animals, is a poor
guide to the likelihood of unwanted effects in humans. (4)
Nevertheless, the therapeutic index emphasizes the importance of the margin
of safety, as distinct from the potency, in determining the usefulness of a drug.
Clinical Implications of pharmacokinetics and
pharmacodynamics

Understanding the pharmacokinetics and pharmacodynamics of drugs is

essential for optimizing drug therapy in clinical practice. Several applications
of these concepts are routinely used in clinical practice, including
individualized dosing, therapeutic drug monitoring, and pharmacogenomic
testing. For example, some drugs may require individualized dosing based on
patient-specific factors, such as renal function or genetic background.
Therapeutic drug monitoring may be used to optimize drug dosing and prevent
toxicity in certain patient populations. Pharmacogenomic testing can help
identify patients who may be at increased risk for adverse drug reactions or
who may require alternative treatments.

1. Dose optimization: Pharmacokinetic and pharmacodynamic data are

used to determine the optimal dose and dosing regimen for a drug. This
includes understanding the relationship between drug concentration and
the resulting pharmacological effect, as well as the factors that affect drug
absorption, distribution, metabolism, and elimination. By optimizing the
dose, drugs can be used more effectively and with fewer adverse effects.
2. Drug-drug interactions: Pharmacokinetic and pharmacodynamic
interactions between drugs can alter the effects of one or both drugs,
leading to adverse effects or reduced efficacy. Understanding these
interactions is critical for safe and effective drug therapy. For example,
some drugs may inhibit or induce the metabolism of other drugs, leading
to changes in their pharmacokinetic properties. Similarly, drugs that
target the same receptors or pathways can interact
pharmacodynamically, leading to enhanced or reduced effects.
3. Therapeutic drug monitoring: Pharmacokinetic and
pharmacodynamic monitoring of drug therapy can help to optimize
dosing and ensure that therapeutic concentrations are maintained. This
is particularly important for drugs with narrow therapeutic windows,
where the difference between therapeutic and toxic doses is small. By
monitoring drug concentrations and pharmacological effects, dosing can
 be adjusted to achieve optimal therapeutic outcomes while minimizing
adverse effects.
4. Personalized medicine: Pharmacokinetic and pharmacodynamic data
can be used to tailor drug therapy to individual patients based on their
unique characteristics, such as age, weight, genetic makeup, and co-
morbidities. This approach, known as personalized medicine, has the
potential to improve drug efficacy and reduce adverse effects by
optimizing dosing and selecting drugs that are most likely to be effective
for a particular patient.
In summary, pharmacokinetics and pharmacodynamics are essential tools in
drug development and clinical practice. By understanding how drugs are
absorbed, distributed, metabolized, and eliminated, and how they interact with
their target molecules to produce a pharmacological effect, pharmacokinetics
and pharmacodynamics can be used to optimize drug therapy and improve
patient outcomes.

References

1. Lalonde RL. Pharmacology and Therapeutics; 2009.

2. Maharjan S. Biopharmaceutical factors affecting Metabolism. ; 2014.

3. Pharmacokinetics - Online content for students. [Online].; 2020. Available from:

https://sepia2.unil.ch/pharmacology/applications/pharmacokinetic-variability/.

4. ToxTutor. [Online].; 2020. Available from: https://www.oraulearning.org/topclass/media/a7ab6ff6-

ccb2-4f0c-80ca-7a56b7015f8a/02-005.html.