Monoclonal antibodies are laboratory-made molecules that are designed to mimic the immune system's ability to fight off harmful pathogens such as viruses and cancer cells. They are created by cloning a single type of immune cell, called a B cell, which produces a specific antibody that can recognize and bind to a particular target molecule or antigen. An antigen can be a foreign molecule that interacts with the cells of the immune system , triggering an immune response. The molecules on the antigens to which the antibodies attach themselves are called Epitopes. The region of the antibody which binds to the Epitope is called a Paratope. 

1. 15-03-2023 ISF COLLEGE OF PHARMACY 1
ABHINAV VASHISHAT [M PHARMACY]
DEPARTMENT OF PHARMACEUTICS
ISF COLLEGE OF PHARMACY, MOGA
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS
Topic:-Pharmacokinetics & Pharmacodynamic of Monoclonal Antibodies

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ISF COLLEGE OF PHARMACY
MONOCLONAL ANTIBODIES
An Antibody is a protein that protect the human body against foreign substances or invading
microorganisms, the immune system has developed several defence mechanisms, the
ultimate goal being to eliminate these potentially harmful interferences from the body.
Monoclonal antibodies are laboratory-made molecules that are designed to mimic the immune
system's ability to fight off harmful pathogens such as viruses and cancer cells. They are
created by cloning a single type of immune cell, called a B cell, which produces a specific
antibody that can recognize and bind to a particular target molecule or antigen.
An antigen can be a foreign molecule that interacts with the cells of the immune system ,
triggering an immune response.
The molecules on the antigens to which the antibodies attach themselves are called Epitopes.
The region of the antibody which binds to the Epitope is called a Paratope.

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The mAb therapeutics currently on the market are from the immunoglobulin G (IgG) isotype
such as IgG1, IgG2, and IgG4, which in general have PK characteristics such as slow
clearance, long half-life, and limited tissue distribution. After intravenous (IV) administration,
typical mAb serum PK profiles are biphasic with a rapid distribution phase and a slower
elimination phase

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Pharmacokinetics (PK) of mAb:-
The pharmacokinetics of monoclonal antibodies (mAbs) is different from that of small
molecules due to their large size and complex structure. Here are the key aspects of the PK
of mAb:-
Absorption
Intravenously Extravascularly
Distribution
MAb
properties
Target
antigen
expression
Tissue
permeability Elimination
Clearance Metabolism
Binding to
Antigen

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Absorption:-
• mAbs are directly injected into the bloodstream.
• Immediate and complete bioavailability of the mAb
Intravenous
Administration
• Dependent on systemic absorption include convective
transport of antibody through lymphatic vessels. The mAbs
enter the lymphatic system by convective flow of interstitial
fluid into the porous lymphatic vessels.
• Diffusion of antibody across blood vessels distributed near
the site of injection.
Extra vascular
Administration
(SC/IM)
• The majority of mAbs that have been approved or are currently in clinical development are
administered by intravenous (IV) infusion. Consequently, extra vascular routes have been chosen as
alternatives, including subcutaneous administration and intramuscular administration.
• The absorption rate can be influenced by factors such as the injection site, formulation, and volume of
the injection.

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• The distribution of monoclonal antibodies (mAbs) refers to the process by which these molecules are
transported throughout the body after entering the bloodstream.
Distribution:-
• If the target antigen is highly expressed in a particular tissue, the mAb may
accumulate in that tissue, leading to higher drug levels and potentially increased
efficacy. On the other hand, if the target antigen is expressed at low levels, the mAb
may not accumulate in that tissue and may be more rapidly cleared from the body.
Target antigen
expression
• Tissues, such as the blood-brain barrier, have limited permeability to large molecules
like mAbs.
Tissue
permeability
• The properties of the mAb itself, such as its size, charge, and hydrophobicity, can
also impact its distribution. For example, mAbs with a higher molecular weight may
be more likely to accumulate in the blood vessels, while mAbs with a higher
hydrophobicity may be more likely to accumulate in fatty tissues.
MAb properties

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Elimination:-
• Elimination half-life can vary depending on factors such as their target, size, and degree of
glycosylation.
• As glomerular filtration has an approximate molecular size limit of 20–
30 kDa, mAbs do not undergo filtration in the kidneys due to their
relatively large size.
• Biliary excretion of mAbs has been reported only for IgA molecules,
and only to a very small extent.
Clearance
• Occurs through proteolysis in the liver and the reticuloendothelial
system (RES). Degradation will be more rapid for more nonhuman
antibodies..
• The lower the nonhuman fraction, the longer the half-life
• murine (few days) < chimeric < humanized < human (few weeks)
Metabolism
• Binding to Antigen Binding of mAbs not only affects distribution but
also reflects another means of elimination. Binding of the Fab region to
the antigen with high affinity must be regarded as almost irreversible.
Binding to
Antigen

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Pharmacodynamics (PD) of mAb:-
• The study of how these molecules interact with their target antigens and other molecules in the body
to produce their therapeutic effects
 Mechanism of action: mAbs exert their effects by binding to specific targets, either on the surface
of cells or in the extracellular space. This binding can lead to a variety of downstream effects, such
as receptor internalization, complement activation, or antibody-dependent cellular cytotoxicity.
 Target expression: The efficacy of mAbs is influenced by the level of target expression on the cell
surface or in the extracellular space. High target expression can increase the binding of mAbs to
their target and enhance their effects, while low target expression can reduce the binding of mAbs
and decrease their efficacy.
Here are the key aspects of the PD of mAbs:

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 Antibody affinity and specificity: The binding of mAbs to their targets is influenced by their affinity and
specificity. High-affinity mAbs can bind more strongly to their targets, leading to increased efficacy.
Specificity refers to the ability of mAbs to bind selectively to their targets, without cross-reacting with
other molecules in the body.
 Immunogenicity: mAbs can trigger an immune response in some patients, leading to the formation of anti-
drug antibodies (ADAs). ADAs can reduce the efficacy of mAbs by neutralizing their effects or increasing
their clearance from the body. The immunogenicity of mAbs can be influenced by factors such as the dose,
frequency of administration, and patient factors such as genetics and immune status.

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Conclusion:-
Understanding the pharmacokinetics and pharmacodynamics of monoclonal antibodies is critical for
optimizing their efficacy and minimizing their potential side effects. The PK of mAbs is influenced by
factors such as absorption, distribution, metabolism, and excretion, while the PD of mAbs is influenced
by their mechanism of action, target expression, antibody affinity and specificity, and immunogenicity.