This document discusses the pharmacokinetics and pharmacodynamics of biotechnological drugs including peptides, proteins, monoclonal antibodies, oligonucleotides, and gene therapy vectors. It covers topics such as absorption, distribution, metabolism, and elimination of these drugs. For peptides and proteins, it describes various administration routes and challenges. For monoclonal antibodies, it discusses effector functions, modes of action, and characteristics. For oligonucleotides, it explains mechanisms of action and pharmacokinetics such as tissue distribution and excretion. Gene therapy methods using viral and non-viral vectors are also summarized.
Biopharmaceutical system , methods of permeability , generic biologics, gener...Siddhapura Pratik
Biopharmaceutical classification system, methods of permeability, generic biologics ( biosimilar drug product), clinical significance of bioequivalence studies , special concerns in bioavailability and bioequivalence studies , Generic substitution
Biopharmaceutical system , methods of permeability , generic biologics, gener...Siddhapura Pratik
Biopharmaceutical classification system, methods of permeability, generic biologics ( biosimilar drug product), clinical significance of bioequivalence studies , special concerns in bioavailability and bioequivalence studies , Generic substitution
Computational modeling of drug dispositionPV. Viji
Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
Computational modelling of drug disposition lalitajoshi9
computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
Computational modeling of drug dispositionPV. Viji
Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
Computational modelling of drug disposition lalitajoshi9
computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
Pharmacokinetics and pharmacodynamics of Biotechnological drugs-SnehalTidke
Pharmacokinetics and pharmacodynamics of biotechnological drugs along with appliations- Proteins and peptides, monoclonal antibodies, oligonucleotides, gene therapy and vaccines
proteins are chains of amino acids, each joined to it
neighbor by a specific type of covalent bond. The
polymerization of L-α-amino acids by peptide
bonds forms the structural framework of proteins. The
term protein is used for molecules composed of over 50
amino acids. The term peptide is used for molecules
composed of less than 50 amino acids.
The chemical and structural complexities involved
demand an effective delivery system in which the
physicochemical and biologic properties, including
molecular size, conformational stability, solubility,
sensitivity to light, moisture and heat, biological half-life,
immunogenicity, dose requirements, susceptibility to
break down in both physical and biological environments,
requirement for specialized mechanisms for transport
across biological membranes are to be considered.
Peptide and Protein Structure
It is essential to have an idea about structure of protein
and peptide in order to deal with various problems
encountered while developing drug delivery system.
The proteins are relatively large molecules with complex
structure. The peptide chains in peptides and proteins are
seldom linear and adapt a variety of specific folded three
dimensional patterns and conformations.
All peptides and proteins are polymers of amino acids
connected via amide linkages referred to as peptide
bonds.
• Primary structure: It denotes the number and
specific sequence of amino acids.
• Secondary structure: Arrangement of individual
amino acids along the polypeptide backbone.
• Tertiary structure: Three dimensional
arrangement of a single protein molecule.
• Quaternary structure: Proteins that contain two
or more polypeptide chains associated by noncovalent
forces
Liquid dosage forms: Advantages and disadvantages of liquid dosage forms. Excipients used in formulation of liquid dosage forms. Solubility enhancement techniques
Good Laboratory Practices: General Provisions, Organization and Personnel, Facilities, Equipment,
Testing Facilities Operation, Test and Control Articles, Protocol for Conduct of a Nonclinical Laboratory
Study, Records and Reports, Disqualification of Testing Facilities, Organization and Personnel, Facilities, Equipment,
Testing Facilities Operation, Test and Control Articles, Protocol for Conduct of a Nonclinical Laboratory
Study, Records and Reports, Disqualification of Testing Facilities
PHARMACEUTICAL QUALITY ASSURANCE SIXTH SEMSTER B PHARM
Introduction, definition and general principles of calibration, qualification
and validation, importance and scope of validation, types of validation, validation master plan. Calibration of pH meter, Qualification of UV-Visible spectrophotometer, General principles of Analytical
method Validation.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
2. INTROUCTION
Biotechnological drugs are the subset of the therapeutic group of biologics.
Therapeutic biologic products, or biologics, are defined by the U.S. Food and
Drug Administration (FDA) as any virus, therapeutic serum, toxin, antitoxin,
or analogous product applicable to the prevention, treatment or cure of
diseases or injuries of man. •Examples:- proteins, monoclonal
antibodies……..
Pharmacokinetics characterize what the body does to the drug.
Pharmacodynamics assesses what the drug does to the body.
3. PHARMACOKINETICS OF PEPTIDE AND
PROTEINS
❑Administration pathways:
Oral administration
•Therapeutically inactive upon oral administration due to
➢High gastrointestinal enzyme activity
➢ low permeability through gastrointestinal mucosa
Administration by injection/infusion
•Achieve the highest concentration in biological system
•There is a reduced bioavailability incase of subcutaneous and intramuscular
route compared to intravenous route
4. The true absorption rate constant Ka in this case Ka=Fkapp F-bioavailability
compared to IV infusion Kapp-apparent absorption rate constant
5. ❖Inhalational administration
•Inhalational delivery of protein peptide offer the advantage of
➢Ease of administration
➢Presence of large surface area available for absorption
➢High vascularity of administration site
➢Bypass of hepatic first pass metabolism
•Disadvantages
➢Presence of certain proteases in lungs
➢Potential local side effect of the inhaled agents on the lung tissue
➢Molecular weight limitation Example:-Inhaled recombinant human insulin
product with
Exubera
Dornase-α-for the treatment of cystic fibrosis
6. ❖Intranasal administration
•intranasal administration of peptides and proteins offers the advantages of
➢ease of administration,
➢delivery to a surface area rich in its vascular and lymphatic network,
➢ bypassing of hepatic first-pass metabolism
•Examples:-calcitonin, oxytocin, LH-RH, growth hormone,intreferone
•Limitation
➢high variability in absorption associated with the site of deposition,
➢ the type of delivery system,
➢changes in mucus secretion and mucociliary clearance,
➢presence of allergy, hay fever, or the common cold in the target population
7. ❖Transdermal administration
•It offers the advantages of bypassing metabolic and chemical degradation in
the gastrointestinal tract, as well as first-pass metabolism by the liver.
• Methods frequently used to facilitate transdermal delivery include
sonophoration and iontophoresis.
•Both methodologies increase skin permeability to ionic compounds
• sonophoration by applying low-frequency ultrasound,
•iontophoresis by applying a low-level electric current.
8. ❖Peroral administration
•Oral delivery of peptides and proteins would be the preferred route of
administration if bioavailability issues could be overcome, as it offers the
advantages of convenient, pain-free administration.
•Methods
➢Use of absorption enhancers
➢Microencapsulation
➢amino acid backbone modification,
➢alternate formulation design,
➢chemical conjugation to improve their resistance to degradation,
➢inhibition of enzymatic degradation by co-administration of protease
inhibitors
9. DISTRIBUTION
The volume of distribution of a peptide or protein drug is determined largely
by its
➢physico-chemical properties (e. g., charge, lipophilicity),
➢protein binding,
➢ dependency on active transport processes.
Due to their large size – and therefore limited mobility through
biomembranes – most therapeutic proteins have small volumes of
distribution, typically limited to the volumes of the extracellular spac
10. After IV application, peptides and proteins usually follow a biexponential
plasma concentration–time profile.
It can be described by a two-compartment pharmacokinetic model.
Central compartment -vascular space and the interstitial space of well-
perfused organs with permeable capillary walls, especially liver and kidneys.
Peripheral compartment - interstitial space of poorly perfused tissues such
as skin and (inactive) muscle
11. ELIMINATION
They are eliminated by metabolism via the same catabolic pathways as
endogenous or dietary proteins, resulting in amino acids.
Non-metabolic elimination pathways such as renal or biliary excretion are
generally negligible for most peptides and proteins.
The elimination of peptides and proteins can occur unspecifically almost
everywhere in the body, or it can be limited to a specific organ or tissue.
➢Proteolysis
•By the action of proteases and peptidases
•Not only limited to the liver, kidneys, and gastrointestinal tissue, but also
include the blood and vascular endothelium as well as other organs and
tissues.
12. ➢Gastrointestinal Elimination
•major site of metabolism
•primary reason for their lack of oral bioavailability
➢Renal elimination
•For parenterally administered and endogenous peptides and proteins
•major elimination organ if the peptide/protein size is less than the glomerular
filtration limit of ~60 kDa
➢Hepatic Elimination
•The rate of hepatic metabolism is dependent on specific amino acid sequences
in the protein.
•Substrates for hepatic metabolism include insulin, glucagon, and t-Pas
•An important first step in the hepatic metabolism of proteins and peptides is
uptake into the hepatocytes.
13. PHARMACOKINETICS OF MONOCLONAL
ANTIBODIES
Monoclonal antibodies have a significant potential as therapeutic agents
because of their ability to bind to specific structures as targets.
This principle of “targeted therapy” results in high clinical efficacy whilst
minimizing adverse reactions, and thus increases mAb tolerability and use.
Example:- Natalizumab (Tysabri) can be used for the treatment of multiple
sclerosis
Antibodies display several different effector functions and modes of action as
part of their function in the human immune system.
14. BIOLOGICAL EFFECTOR FUNCTIONS OF MABS
Antibody-dependent cellular cytotoxicity by natural killer (NK) cells.
Complement-dependent cytotoxicity (CDC).
Neutralization of exotoxins and viruses.
Prevention of bacterial adherence to host cells.
Membrane attack complex (MAC) resulting in cytolysis.
Agglutination of microorganisms.
Immobilization of bacteria and protozoa.
Opsonization.
15. MODES OF ACTION OF MABS
Antibody-Dependent Cellular Cytotoxicity (ADCC)
Complement-Dependent Cytotoxicity
Blockage of Interaction between (Patho)Physiological Substance and
Antigen
Conjugated Unlabeled mAbs
16. PHARMACOKINETIC CHARACTERISTICS OF
mABS
➢Absorption
Due to their high molecular mass (and other reasons), the vast majority of
mAbs are administered by intravenous (IV) infusion.
IV infusions represent the most inconvenient as well as time- and cost-
consuming means of administration.
Hence extravascular routes have been chosen as alternatives, including
subcutaneous administration (SC; e. g., adalimumab, efalizumab) and
intramuscular administration (IM; e. g., palivizumab).
The mechanism of absorption after SC or IM administration is thought to
occur via the lymphatic system.
17. ➢Distribution
The distribution of classical mAbs in the body is poor.
Limiting factors are, in particular, the high molecular mass and the
hydrophilicity/polarity of the molecules
➢Transport
Permeation of mAbs across the cells or tissues is accomplished by transcellular
or paracellular transport.
It involve the processes of diffusion, convection, and cellular uptake.
Due to their physico-chemical properties, the extent of passive diffusion of
classical mAbs across cell membranes in transcellular transport is minimal.
Cellular uptake of mAbs takes place via endocytosis and can be either receptor
mediated,or non-receptor-mediated
18. ➢Volume of Distribution
The estimated volumes of distribution are small and relatively homogeneous.
small-sized antibody fragments can penetrate tissues more easily, might
potentially cross the blood–brain barrier, and can be delivered locally to the
lung through inhalation.
➢Elimination
Clearance
✓mAbs do not undergo filtration in the kidneys due to their relatively large size.
✓renal elimination in total is uncommon or low for mAbs.
✓Biliary excretion of mAbs has been reported only for IgA molecules,and only to
a very small extent
19. Major elimination routes are
➢Proteolysis
➢Binding to antigen
➢Binding to anti-idiotype antibodies
20. PHARMACOKINETICS AND PHARMACODYNAMICS
OF OLIGONUCLEOTIDES
A polynucleotide whose molecules contain a relatively small number of
nucleotides.
It include antisense oligonucleotides (ASO), RNA interference (RNAi), and
aptamer RNAs.
ASO and RNAi oligonucleotides are intended mainly for modulating gene
and protein expression.
Aptamer oligonucleotides can act as “chemical antibodies” to modulate
functions of proteins and other macromolecules.
21. PHARMACOKINETICS:
❖Absorption
The primary route of administration for antisense oligonucleotides for systemic
applications is by parenteral injection, either intravenous (i.v.) infusion or
subcutaneous injection.
The plasma half-life following SC administration is longer than that after IV
injection, and is indicative of continued absorption from the injection site during
the disposition phase.
Topical or local application of oligonucleotides generally results in localized
distribution and activity.
Oligonucleotides do not cross the blood–brain barrier (BBB) following systemic
administration .
But it can be directly injected or infused into the cerebrospinal fluid with resultant
broad distribution to spinal cord and brain
22. ❖Distribution
The highest tissue accumulation has been observed in kidney, liver, spleen,
lymph nodes, adipocytes and bone marrow
oligonucleotides that lack charge are less extensively or more weakly bound
to plasma proteins exhibit more rapid clearance from blood primarily due to
either metabolism in blood or excretion in urine.
At clinically relevant concentrations in plasma, saturation of binding does not
occur.
Topical or local application of oligonucleotides generally results in localized
distribution and activity
23. ❖Metabolism:
Oligonucleotides are metabolized by nucleases
It do not serve as substrates for P450 oxidative metabolism.
Parent drug and its nuclease generated smaller oligonucleotide fragments
are excreted in urine.
❖Excretion
Oligonucleotides and their shortened oligonucleotide metabolites are
excreted primarily in urine.
24. PHARMACODYNAMICS:
They inhibit gene expressions sequence-specifically by hybridization to
mRNA through Watson–Crick base pair interactions.
Degradation of the target mRNA through an RNase Hdependent terminating
mechanism.
Finally it prevents translation of the encoded protein product, or the disease-
causing factor in a highly sequence-specific manner.
Example:-Fomivirsenfor the treatment of cytomegalovirus retinitis in patients
withAIDS Mipomersen for the treatment of homozygous familial
hypercholesterolaemia (HoFH), a rare genetic disorder that leads to
excessive levels of low-density lipoprotein (LDL) cholesterol.
25. GENE THERAPY
Definiton: an experimental technique for correcting defective genes that are
responsible for disease development.
The most common form of gene therapy involves inserting a normal gene to
replace an abnormal gene
Gene therapy utilizes the delivery of DNA into cells, which can be
accomplished by a number of methods.
The two major classes of methods : recombinant viruses – VIRAL VECTOR
naked DNA or DNA complexes –
❑NONVIRAL VECTOR
26. ❖Naked DNA
It is generally difficult to determine pharmacokinetic parameters for naked
DNA as it is rapidly and extensively degraded in plasma.
The clearance from plasma after IV administration is even more rapid.
After intramuscular and intradermal injections of naked plasmid showed that
DNApersisted at the injection site and in lymph nodes up to 28 days after
injection.
❖Non-Viral Vectors
Chemical vectors include polycationic carriers such as liposomes
(lipoplexes) and polymers (polyplexes).
These carriers avoid the DNAsize limitations and immunogenicity associated
with viral vectors
27. After administration, non-viral vectors encounter resistance due to the barriers in
gene delivery
❑Systemic barriers
degradation of DNAby plasma nucleases,
Opsonization of DNA complexes by negatively charged serum components,
Uptake by the reticuloendothelial system
Distribution of DNA to non-target tissues
❑Cellular barriers
Internalization at the cell surface
Endosomal release
Cytoplasmic degradation
Translocation into the nucleus
28. In lipoplex DNA is usually encapsulated inside the liposome. Although this is
beneficial in that it protects the DNAfrom degradation. 3 types of lipids:
anionic (negatively charged)
neutral
cationic (positively charged).
Polyplex are the Complexes of polymers with DNA.
Consist of cationic polymers and their production is regulated by ionic
interactions.
29. ❖Viral Vectors
Recombinant adeno-associated virus (rAAV) has been widely used as a
therapeutic gene delivery vector.
It binds to both heparin sulfate proteoglycans and fibroblast growth factor
receptors as an essential step for cellular entry.
This accounts for their different biodistribution properties when injected into brain
and other tissues
The pharmacokinetic properties of a vector depend on
✓route and duration of administration,
✓the dose,
✓The physical properties of the vector (e. g., size),
✓ cell-tropism.
30. IV administration of rAAV generally results in the vector accumulating
primarily in the liver, although smaller amounts spread to many tissues
including the spleen, smooth muscle, striated muscle and kidneys.
The route of vector administration affected its spread and distribution.
Elimination of viral vectors within tissues or within the blood compartment
results from the action of both endonucleases and exonucleases.
Intramuscular injection resulted in high and localized transgene production
especially in the liver, while IV injection produced low expression in this
tissue.
31. CONCLUSION
Advances in biotechnology have triggered the development of numerous
new drug products.
Biotechnological drugs include not only therapeutically used peptides and
proteins, including monoclonal antibodies, but also oligonucleotides and
DNApreparations for gene therapy.
The dose–concentration–effect relationship is defined by the
pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of a drug.
PK/PD concepts in all stages of preclinical and clinical drug development is
one potential tool to enhance the information gain during drug development.
PK/PD analysis supports the identification and evaluation of drug response
determinants.
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