The document discusses bioavailability and bioequivalence. It defines bioavailability as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action. Bioequivalence is achieved when two drug products containing the same active ingredient have the same rate and extent of absorption. The document outlines factors that affect bioavailability such as pharmaceutical, patient, and route of administration factors. It also describes various methods to measure bioavailability including pharmacokinetic and pharmacodynamic approaches.
A brief presentation on the factors affecting bioavailability of drugs along with a quick overview on what is bioequivalence, clinical equivalence, therapeutic equivalence, chemical equivalence and pharmaceutical equivalence.
A brief presentation on the factors affecting bioavailability of drugs along with a quick overview on what is bioequivalence, clinical equivalence, therapeutic equivalence, chemical equivalence and pharmaceutical equivalence.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Measurement of bioavailability and concept of equivalenceRavish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
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Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
Lecture Presentation in Basic Intravenous Therapy Seminar talks on Basic Pharmacology, the pharmacodynamics and pharmacokinetics, the common IV medications used, precautions and interactions of medications
General Pharmacology Lecture Slides on Bioavailability and Bioequivalence by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
A geographical indication (GI) is a name or sign used on certain products which corresponds to a specific geographical location or origin (e.g. a town, region, or country)
Examples: Basmati rice, Swiss watches etc
Design, optimization and in vitro evaluation of gastroretentive hollow micros...SURYAKANTVERMA2
To modify the GIT time is one of the main challenge in the development of oral controlled drug delivery system.
Gastric emptying of pharmaceutical dosage form is highly variable and dependent on the dosage form and the fed/fasted state of the stomach.
Normal gastric residence time usually ranges between 5 minutes to 2 hours.
Formulation and evaluation of fast dissolving tabletsSURYAKANTVERMA2
The concept of mouth dissolving drug delivery systems (MDDDS) or fast dissolving tablets emerged with an objective to improve patient’s compliance.
These dosage forms rapidly disintegrate and/or dissolve to release the drug as soon as they come in contact with saliva, thus obviating the need for water during administration, an attribute that makes them highly attractive for pediatric and geriatric patients.
Microsoft Windows, or simply Windows, is a metafamily of graphical operating systems developed, marketed, and sold by Microsoft. It consists of several families of operating systems, each of which cater to a certain sector of the computing industry with the OS typically associated with IBM PC compatible architecture. Active Windows families include Windows NT and Windows Embedded; these may encompass subfamilies, e.g. Windows Embedded Compact (Windows CE) or Windows Server. Defunct Windows families include Windows 9x, Windows Mobile and Windows Phone.
The greenhouse effect is a process by which thermal radiation from a planetary surface is absorbed by atmospheric greenhouse gases, and is re-radiated in all directions.
“A GMP is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product”.
Introduction to environment and environmental studiesSURYAKANTVERMA2
“Environmental studies” is the scientific study of our environment and our place in it.
Definition: “Environmental studies” is the study of environmental issues.
It has broader coverage than environmental science and includes social aspects of environment also.
Natural resources are materials and components (something that can be used) that can be found within the environment. Every man-made product is composed of natural resources (at its fundamental level). A natural resource may exist as a separate entity such as fresh water, and air, as well as a living organism such as a fish, or it may exist in an alternate form which must be processed to obtain the resource such as metal ores, oil, and most forms of energy.
Environmental Pollution can be defined as any undesirable change in physical, chemical, or biological characteristics of any component of the environment i.e. air, water, soil which can cause harmful effects on various forms of life or property.
Pollution: The term pollution can be defined as influence of any substance causing nuisance, harmful effects, and uneasiness to the organisms
Pollutant: Any substance causing Nuisance or harmful effects or uneasiness to the organisms, then that particular substance may be called as the pollutant.
EnvironmentalPollutioncanbedefinedasanyundesirablechangeinphysical,chemical,or biological characteristics of any component of the environment i.e.air,water, soil which can cause harmful effects on various forms of life or property.
Water (prevention and control of pollution) act, 1974SURYAKANTVERMA2
AnActtoprovideforthepreventionandcontrolofwaterpollutionandthemaintainingorrestoringofwholesomenessofwater,for the establishment, with a view to carrying out the purposes aforesaid, of Boards for the prevention and control of water pollution,forconferringonandassigningtosuchBoardspowersandfunctionsrelatingtheretoandformattersconnectedtherewith.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
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
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!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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
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.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
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
4. Regulatory Definition (21 CFR 320.1(a)):
“ Bioavailability-
means the rate and extent to which the
active ingredient or active moiety is absorbed
from a drug product and becomes available at
the site of action."
Or
“Bioavailability is defined as rate and extent
of absorption of unchanged drug from it’s
dosage form and become available at the site
of action.” 4
5. Primary stages of development of a suitable dosage
form for new drug entity.
Determination of influence of excipients, patient related
factors and interaction with other drugs on the
efficiency of absorption.
To evaluate the absolute systemic availability of active
drug substance from a dosage form.
Control quality of drug in early stages of development.
Develop new formulation for existing drug.
5
6. Systemic availability the amount that reaches
systemic circulation is simply known as availability.
Absolute bioavailability of a drug product may be
comparing the respective bioavailabilites after an
oral and iv bolus injection.
Relative bioavailability is defined as a ratios of
bioavilabilities of a drug product and reference
standard.
6
8. Route Bioavailability (%) Characteristics
Intravenous (IV) 100 (by definition) Most rapid onset
Intramuscular (IM) 75 to ≤ 100 Large volumes often possible;
may be painful
Subcutaneous (SC) 75 to ≤ 100 Smaller volumes than IM; may
be painful
Oral (PO) 5 to < 100 Most convenient; first pass
effects may be significant
Rectal (PR) 30 to < 100 Less first-pass effects than oral
Inhalation 5 to < 100 Often very rapid onset
Trans-dermal 80 to ≤ 100 Usually very slow absorption;
used for lack of first-pass
effects; prolonged duration of
action.
9. 9
Three major factors that effecting bioavailability:-
1. Pharmaceutical factors
2. Patient related factors
3. Routes of administration.
11. 1.Pharmaceutical factors:
Physicochemical properties of the drug.
1. Particle size
2. Crystalline structure
3. Salt form
Pharmaco - Technical Factors or Formulation
and manufacturing variables.
1.Disintegration and dissolution time
2.Pharmaceutical ingredients
3.Special coatings
4.Nature and type of dosage form
0
12. 2. Patient related factors:
Physiologic factors.
1.Variations in pH of GI fluids
2.Gastric emptying rate
3. Intestinal motility
4. Pre-systemic and first-pass metabolism
5. Age, sex
6. Disease states
Interactions with other substances.
1. Food
2. Fluid volume
3. Other drugs
3. Route of administration:
1.Parentral administration
2.Oral administration
3.Rectal administration
4.Topical administration 0
13. The methods available are:-
Pharmacokinetic (Indirect) Method
Pharmacodynamic (Direct) Method.
Selection of method depends upon :-
Nature of The Study
Nature of Dosage Form
Analytical Method Development.
10
15. Widely used and based on assumption that
Pharmacokinetic profile reflects the therapeutic
effectiveness of a drug.
Plasma Level- Time Studies:
Most common type of human bioavailability studies.
Based on the assumption that there is a direct
relationship between the concentration of drug in blood
or plasma and the concentration of drug at the site of
action.
Following the administration of a single dose of a
medication, blood samples are drawn at specific time
intervals and analyzed for drug content.
0
16. A profile is constructed showing the concentration of
drug in blood at the specific times the samples were
taken.
Bioavailability (the rate and extent of drug
absorption) is generally assessed by the determination
of following three parameters.
They are..
1. Cmax (Peak plasma concentration)
2. Tmax (time of peak)
3. AUC (Area under curve)
10
18. Cmax - Maximum plasma concentration.
1.The concentration of drug at therapeutic response is elicited.
2.Increase with increase in dose and with an increase in
absorption.
3.Expressed in terms of μg/ml or mg/ml.
Tmax-Time to reach maximum concentration
1.Indicates rate of absorption.
2.It decrease as the rate of absorption increases.
3.Expressed in terms of hours or minutes.
AUC - Area under thecurve.
1.Indicates the extent of drug absorption from a dosage form.
2.The fraction of dose that reaches the systemic circulation.
18
19. MEC: The minimum plasma concentration of the drug
required to achieve a given pharmacological or therapeutic
response.
MSC: Plasma concentration of the drug beyond which
adverse effects are likely to happen.
THERAPEUTIC RANGE: The range of plasma drug
concentration in which the desired response is achieved yet
avoiding adverse effect. The aim is clinical practice is to
maintain plasma drug concentration within the therapeutic
range.
ONSET OF ACTION: On set of action is the time
required to achieve the minimum effective plasma
concentration following administration of drug formulation.19
20. DURATION OF ACTION- Duration of action of
the therapeutic effect of the drug is defined as the
time period during which the plasma concentration of
the drug exceeds the minimum effective level.
INTENSITY OF ACTION- In general, the
difference between the peak plasma concentration
and the minimum effective plasma concentration
provides a relative measure of the intensity of the
therapeutic response of the drug.
20
21. The extent of bioavailability is
calculated from equation :
For single dose study:
21
22. Urinary Excretion Studies:
Urinary excretion of unchanged drug is directly
proportional to plasma concentration of drug.
Thus, even if a drug is excreted to some extent (at least
10 to 20%) in the urine, bioavailability can be
determined. eg: Thiazide diuretics, Sulphonamides.
Method is useful when there is lack of sufficiently
sensitive analytical technique to measure drug
concentration.
Noninvasive method, so better patient compliance.
0
24. Maximum urinary excretion rate
• Its value increases as rate and/or extent of absorption increases.
• It is obtained from peak of plot between rate of urinary
excretion data versus time of urine collection period.
Time for maximum excretion rate
• It is the maximum time required to reach maximum excretion
rate.
• Its value decreases as absorption rate increases.
• Analogues of tmax of plasma level data.
Cumulative amount of drug excreted (X)u∞
• It is the drug excreted in urine till the drug level fallszero.
Related to AUC of plasma level data.
• It increases as the extent of absorption increases. 24
25. The extent of bioavailability is calculated from
equation:
25
26. Sr. No Plasma data Urinary data
1. Maximum plasma
concentration
C max
Maximum urinary excretion
rate
2. Time to maximum
concentration
T max
Time to maximum
excretion rate
3. Area under the curve
AUC
Cumulative amount of drug
excreted
26
28. Acute pharmacological response
When bioavailability measurement by pharmacokinetic
method is difficult, an acute pharmacologic effect are taken
into consideration.
Dose response curve Can be determined by construction of
Pharmacological effect Vs Timecurve.
E.g.: pupil diameter, heart rate or BP can be useful as an index
of drug Bioavailability.
Disadvantage:
• It tends to be more variable.
• Observed response may be due to an active metabolite
whose concentration is not proportional to concentration of
parent drug.
18
29. Clinical response / Therapeutic response
•Best method Clinical response of the drug for which it is
intended to be used is measured.
•Based on clinical response to the drug formulation given to
the patients
E.g.: for anti-inflammatory drugs, reduction in inflammation is
determined
Drawbacks:
The major drawbacks of this method is that quantitation of observed
response is too improper to allow for reasonable assessment of
relative bioavailability between two dosage forms of the same drug.
18
31. Bioequivalence
When the drug from two or more similar dosage form
reaches the general circulation at the same relative rate
and extent then the dosage forms are termed as
Bioequivalent.
Statistical significant differences are observed in the
bioavailability of two or more drug products,
termed as Bio-inequivalence.
20
32. 1. A comparison of the bioavailability of two or more
drug products.
2. Two products or formulations containing the same
active ingredient are bioequivalent if their rates and
extents of absorption are the same.
3. Bioequivalence may be demonstrated through in
vivo
or
in vitro test methods, comparative clinical trials, or
pharmacodynamic studies.
20
34. Bioequivalence: IR Products
Reference Test
Pharmaceutical Equivalent
Products
Possible Differences
Drug particle size, ..
Excipients
Manufacturing process
Equipment
Site of manufacture
Batch size ….
Documented Bioequivalence
= Therapeutic Equivalence
(Note: Generally, same dissolution spec.)
Normal healthy subjects
Crossover design
Overnight fast
Glass of water
90% CI within 80-125%
of Ref. (Cmax & AUC)
35. When significant changes are made in the manufacture of the
marketed formulation.
When a new generic formulation is tested against the
innovator's marketed product.
Comparison of availability of drug substance from different
dosage forms.
when changes in formulation have occurred after an
innovator product has been approved.
Comparison of availability's of same dosage formproduced
by different manufactures. 21
37. Equivalence may be defined in several ways:
Chemical equivalence:
If two or more dosage forms of same drug contain same labeled
quantities specified in pharmacopoeia. Eg : Dilantin and Eptoin
chemically equivalent as they contain same quantity of
Phenytoin on chemical assay.
Bioequivalence:
The drug substance in two or more identical dosage forms,
reaches the systemic circulation at the same relative rate and
extent i.e. their plasma concentration-time profiles will be
identical without significant statistical differences.
38. Pharmaceutical equivalents:
Drug products in identical dosage forms that contain same active
ingredient(s), i.e , the same salt or ester, are of the same dosage
form, use the same route of administration, and are identical in
strength or concentration.
Eg : Chlordiazepoxide hydrochloride,5mg capsules.
Pharmaceutical equivalent drug products are: Same in :
•Active ingredient and it’s quantity
•Dosage form
•Standards like strength, quality , purity and identity.
•Disintegration time
•Dissolution rates
Differ in:
•Shape
•Release mechanisms
•Packing
•Excipients(including colours , flavours , preservatives)
•labeling
39. Pharmaceutical alternatives:
•Drug product that contain the same therapeutic moiety but as
different salts, esters or complexes.
Eg: Tetracyclin phosphate or Tetracyclin hydrochloride equivalent to
250mg.
Therapeutic equivalents:
•Drug products consider to be therapeutic equivalence only if they are
pharmaceutical equivalence and if they can be expected to have a
same clinical effect and safety profile when administered to patient
specified in the labeling.
•FDA classifies as therapeutically equivalent those products that meet
the fallowing general criteria:
1)They approved as safe and effective.
2)They are pharmaceutically equivalents.
3)They are bioequivalence.
4)They are adequately labeled .
5)They are manufactured in compliance with current GMP regulations.
40. Therapeutic alternatives:
•Drug products containing different active ingredients that are
indicated for the same therapeutic or clinical objectives.
Eg:
1. Ibuprofen is given instead of Aspirin.
2. Cimetidine instead of Ranitidine.
Therapeutic substitution:
•The process of dispensing a therapeutic alternative in place of
the prescribed drug product.
Eg:
1. Ampicillin is dispensed instead of Amoxicillin.
2. Ibuprofen is dispensed instead of Naproxen.