Unit-5 Application of Pharmacokinetic

Modified-Release Drug Product

Modified-release drug products (MRDPs) are special types of medicines that do not release the drug
immediately after you take them. Instead, they are designed to control how fast, where, and for how
long the drug is released in the body.

Types of Modified-Release Drug Product

1.Extended-Release (ER) / Sustained-Release (SR)

- Drug is released slowly over a long time (e.g., 12 or 24 hours).

- Reduces the number of doses needed per day.

- Example: Metformin SR (used for diabetes).

2. Controlled-Release (CR)

- Drug is released at a constant rate for a specific period.

- Helps maintain a steady level of drug in the blood.

- Example: Theophylline CR** (used for asthma).

3. Delayed-Release (DR)

- Drug release is delayed for a certain time, often to protect the drug from stomach acid.

- Example: Enteric-coated aspirin (prevents stomach irritation).

4. Pulsatile Release

- Drug is released in pulses at specific times instead of continuously.

- Useful for diseases that follow a natural rhythm (e.g., hormonal drugs).

5. Targeted-Release

- Drug is delivered to a specific organ or tissue in the body.

- Example: Colon-targeted mesalamine (for ulcerative colitis).

Target Drug Delivery System

Targeted Drug Delivery Systems (TDDS) are advanced drug formulations that deliver a drug directly to
a specific site (organ, tissue, or cells) in the body. This approach minimizes side effects and enhances
drug effectiveness.

Why is Targeted Drug Delivery Important?

Reduces side effects → Only affects the intended area.

Increases drug effectiveness → More drug reaches the disease site.

Lower drug dose required → Reduces toxicity.

Improves patient compliance → Less frequent dosing.

Types of Targeted Drug Delivery Systems

1.Passive Targeting

Uses the natural properties of the body to accumulate drugs in specific areas.

Example: Cancer chemotherapy – Tumor tissues have leaky blood vessels, allowing nanoparticles or
liposomes to accumulate there (Enhanced Permeability and Retention – EPR Effect).

2.Active Targeting

Uses special ligands (antibodies, peptides) that bind to specific receptors on diseased cells.

Example: Monoclonal antibody-based drugs (e.g., Trastuzumab for breast cancer) target cancer cells
without harming healthy cells.

3.Physical Targeting

Uses external forces like heat, magnetic fields, or ultrasound to guide drug delivery.

Example: Magnetic nanoparticles are directed to tumors using external magnets.

Types of Drug Carriers Used in TDDS

4.Liposomes

Small fat-based vesicles that carry drugs inside.

Protects the drug from degradation and reduces toxicity.

Example: Doxil® (Doxorubicin liposome) for cancer treatment.

5.Nanoparticles

Very small particles (1–100 nm) that improve drug absorption and targeting.

Used for anticancer and antiviral drugs.

6.Microspheres & Microcapsules

Tiny biodegradable spheres that slowly release the drug over time.

Example: Lupron Depot (Leuprolide microspheres) for prostate cancer.

7.Antibody-Drug Conjugates (ADCs)

Drug molecules are attached to antibodies that specifically bind to disease cells.

Example: Brentuximab Vedotin for lymphoma.

8.Prodrugs

Inactive drugs that become active only in the target tissue.

Example: Capecitabine (becomes active in cancer cells).

Applications of Targeted Drug Delivery

1).Cancer therapy (Reduces harm to healthy cells).

2).Brain targeting (Overcomes the Blood-Brain Barrier – e.g., Alzheimer’s treatment).

3).Gene therapy (Delivers genetic material to correct mutations).

4).Infectious diseases (HIV, tuberculosis).

5).Would you like more details on a specific type or application?

Biotechnological products
Biotechnological products are pharmaceuticals derived from biological sources using genetic
engineering, cell culture, or fermentation. They include proteins, antibodies, vaccines, gene therapies,
and cell-based treatments.

1. Types of Biotechnological Products

(A) Recombinant Proteins

These are artificially produced proteins using recombinant DNA technology.

Example: Human Insulin (Humulin) – Used in diabetes treatment.

Process: The insulin gene is inserted into bacteria (E. Coli), which produce insulin in large amounts.

(B) Monoclonal Antibodies (mAbs)

These are lab-made antibodies that target specific diseases like cancer, rheumatoid arthritis, and viral
infections.

Example: Rituximab – Used in cancer and autoimmune diseases.

Process: Hybridoma technology is used to produce monoclonal antibodies in large quantities.

(C) Vaccines

Vaccines stimulate the immune system to protect against diseases.

Example: Hepatitis B vaccine – Produced using yeast cells.

Types of Vaccines:

Live-attenuated – Weakened virus (e.g., MMR vaccine).

Inactivated – Killed virus (e.g., Polio vaccine).

Recombinant – Made using genetic engineering (e.g., HPV vaccine).

(D) Gene Therapy Products

These involve inserting, removing, or altering genes inside cells to treat diseases.

Example: Luxturna – A gene therapy for inherited eye disease.

Process: A functional gene is delivered using a viral vector into the patient’s cells.
(E) Cell Therapy Products

Living cells are used to repair, replace, or regenerate damaged tissues or organs.

Example: CAR-T cell therapy – Used in blood cancers like leukemia.

Process: Patient’s T-cells are genetically modified to attack cancer cells.

Introduction to Pharmacokinetic and Pharmacodynamic

Pharmacokinetics (PK) – “What the Body Does to the Drug”

Pharmacokinetics describes how a drug moves through the body after administration. It includes four
main processes:

1).Absorption

The process by which the drug enters the bloodstream from the site of administration (e.g., stomach,
intestines).

Factors affecting absorption: drug formulation, solubility, food, and pH of the stomach.

2).Distribution

After absorption, the drug is transported through the bloodstream to different tissues and organs.

Influenced by factors like blood flow, protein binding, and tissue permeability.

3).Metabolism (Biotransformation)

The drug is chemically converted into active or inactive forms, mostly in the liver.

Enzymes (like cytochrome P450) help in metabolism.

4).Excretion

The drug and its metabolites are removed from the body through urine (kidneys), bile (liver), sweat, or
breath.

These four processes together determine how long a drug stays in the body and at what
concentration.

Pharmacodynamics (PD) – “What the Drug Does to the Body”

Pharmacodynamics explains how drugs produce their effects by interacting with biological targets
such as:

1).Drug-Receptor Interaction

Most drugs bind to specific receptors on cells to activate or block biological responses.

Example: Painkillers like morphine bind to opioid receptors to reduce pain.

2).Dose-Response Relationship

The effect of a drug increases as the dose increases up to a certain limit.

Too much drug can cause toxicity, while too little may not have any effect.
3).Mechanism of Action

Drugs can act by stimulating (agonists) or inhibiting (antagonists) receptors.

Some drugs act on enzymes, ion channels, or DNA to produce effects.

Drug interactions
A drug interaction happens when one drug affects the action of another drug, food, or substance in
the body. This can increase or decrease the effect of a drug or cause side effects.

Types of Drug Interactions

Drug-Drug Interactions

Synergism: Two drugs work together for a stronger effect.

Example: Painkillers with caffeine work better.

Antagonism: One drug reduces or blocks the effect of another.

Example: Antibiotics reduce the effect of birth control pills.

Increased Side Effects: Two drugs with similar effects can increase side effects.

Example: Alcohol + sleeping pills = extreme drowsiness.

Drug-Food Interactions

Some foods can change drug absorption or metabolism.

Example: Grapefruit juice increases the effect of some blood pressure drugs, causing toxicity.

Drug-Disease Interactions

Some drugs can worsen certain medical conditions.

Example: Painkillers (NSAIDs) can increase blood pressure in hypertensive patients.

Pharmacokinetic and Pharmacodynamic of biotechnology drug

Pharmacokinetics (PK) of Biotechnological Drugs

Pharmacokinetics describes what the body does to a drug. For biotechnological drugs (e.g.,
monoclonal antibodies, recombinant proteins), PK is different from small molecules due to their large
size and specific metabolism.

Absorption – Most biotech drugs are given intravenously (IV) because they are large molecules that
are poorly absorbed orally. If given subcutaneously (SC) or intramuscularly (IM), absorption is slow
and depends on lymphatic uptake.

Distribution – These drugs have limited distribution (mostly in plasma and extracellular fluid) due to
their large size and hydrophilic nature. They do not cross cell membranes easily.

Metabolism – Unlike small drugs, biotechnological drugs are broken down by proteolysis (enzymatic
degradation) rather than liver enzymes (CYP450).
Excretion – Cleared by target-mediated elimination (binding to specific receptors) or by
reticuloendothelial system (RES) in the liver and spleen. Some small peptides are filtered by the
kidneys.

Pharmacodynamics (PD) of Biotechnological Drugs

Pharmacodynamics describes what a drug does to the body. Biotech drugs often work through
specific target binding and modulation of biological pathways.

High Specificity – Most biotech drugs (e.g., monoclonal antibodies) bind to a specific receptor or
antigen, reducing side effects.

Prolonged Action – Due to slow elimination, these drugs have a longer duration of action. Some
require weekly or monthly dosing.

Immune System Involvement – Many biotech drugs modify the immune system (e.g.,
immunotherapy for cancer), which can lead to immunogenic reactions (antibody formation against
the drug).

Delayed Response – Unlike small drugs, the effect of biotech drugs may take days to weeks to show
because they influence complex biological processes.

Proteins and Peptides

Definition & Structure

Proteins and peptides are biological macromolecules composed of amino acids linked by peptide
bonds.

Peptides: Short chains (<50 amino acids).

Proteins: Larger polypeptides with complex structures.

1).Pharmaceutical Importance

Hormonal Therapies: Insulin (diabetes), Growth hormone (GH deficiency).

Monoclonal Antibodies: Rituximab (cancer), Adalimumab (autoimmune diseases).

Enzyme Replacement Therapy: Factor VIII (hemophilia), Pancreatic enzymes.

Antimicrobial Peptides: Defensins, peptide-based antibiotics.

Advantages as Drugs

High specificity to target receptors.

Low toxicity and minimal side effects.

Highly potent even in small doses.

Challenges in Drug Delivery

Poor Oral Bioavailability: Degradation by digestive enzymes (pepsin, trypsin).

Short Half-Life: Rapid clearance via kidney filtration or enzymatic breakdown.

Immunogenicity: Risk of immune response with repeated use.

Drug Delivery Strategies

Parenteral Routes: IV, SC, IM (e.g., insulin, erythropoietin).

Modified Release:

PEGylation: Prolongs half-life (e.g., Peginterferon).

Microspheres/Nanoparticles: Protects peptides from degradation.

Liposomes: Targeted delivery and stability enhancement.

Non-Parenteral Routes:

Nasal Delivery: Desmopressin (diabetes insipidus).

Pulmonary Delivery: Insulin (Afrezza).

Transdermal Patches: Limited due to large molecular size.

Biotechnological Approaches

Recombinant DNA Technology: Produces biologics like insulin, monoclonal antibodies.

Protein Engineering: Improves stability, specificity, and therapeutic effects.

Development of oral peptide formulations (nanocarriers, enzyme inhibitors).

Advancements in gene therapy and bioengineered proteins.

Improved targeted delivery systems for enhanced efficacy

Monoclonal antibodies
Monoclonal antibodies (mAbs) are lab-made proteins that act like natural antibodies in your immune
system. They are designed to find and attach to specific targets, such as viruses, cancer cells, or
harmful proteins in the body.

Target Specificity: Each monoclonal antibody is created to recognize one specific molecule (antigen)
on a cell or virus.

Binding: Once they attach to their target, they can block harmful effects, mark the target for
destruction, or trigger the immune system to attack it.

Types of Actions:

Neutralizing toxins or viruses (e.g., COVID-19 treatment).

Blocking harmful signals (e.g., in autoimmune diseases).

Helping the immune system destroy cancer cells (e.g., cancer immunotherapy).

Uses of Monoclonal Antibodies:

Cancer Treatment (e.g., Rituximab for lymphoma).

Autoimmune Diseases (e.g., Adalimumab for rheumatoid arthritis).

Infections (e.g., Palivizumab for RSV in infants).

Oligonucleotides
Definition: Short DNA or RNA molecules used for therapeutic or research purposes.

Function: They can silence, modify, or regulate gene expression.

Types:

Antisense Oligonucleotides (ASOs): Bind to mRNA and block protein production.

Small Interfering RNA (siRNA): Degrades target mRNA to stop protein synthesis.

Aptamers: Bind to proteins and affect their function.

Uses: Treat genetic diseases, cancers, and viral infections.

Example: Nusinersen for spinal muscular atrophy (SMA).

Vaccines (Immunotherapy)
Definition: Biological preparations that stimulate the immune system to fight diseases.

Types:

Live Attenuated: Weakened form of a virus/bacteria (e.g., MMR vaccine).

Inactivated: Killed virus/bacteria (e.g., polio vaccine).

Subunit/Protein-based: Only parts of the pathogen (e.g., HPV vaccine).

mRNA Vaccines: Teach cells to produce viral proteins (e.g., COVID-19 vaccines).

Viral Vector Vaccines: Use harmless viruses to deliver genetic material (e.g., AstraZeneca COVID-19
vaccine).

Immunotherapy: Uses the immune system to treat diseases, especially cancer.

Example: Checkpoint inhibitors (e.g., pembrolizumab) help the immune system attack cancer cells.

Gene Therapies
Definition: Treatment that modifies or replaces faulty genes to cure diseases.

Techniques:

Gene Replacement: Introduces a functional gene to replace a defective one.

Gene Silencing: Stops harmful gene expression (e.g., siRNA therapies).

Genome Editing: Modifies DNA using CRISPR-Cas9 technology.

Delivery Methods:

Viral Vectors: Use viruses to insert genes (e.g., AAV, lentivirus).

Non-viral Methods: Lipid nanoparticles, electroporation.

Uses:

Treat genetic disorders (e.g., sickle cell disease, cystic fibrosis).

Cancer therapy (CAR-T cell therapy).

Some inherited blindness conditions.

Example: Zolgensma for spinal muscular atrophy.