Bioavailability and bioequivalence
Bioavailability-
Whenever a drug is given by oral route it has to go through certain pathway to reach the systemic circulation. Eg. If 100 mg drug is given orally, and if 80 mg is absorbed and 20 mg gets excreted then 80 mg absorbed drug reaches liver through portal system. In liver it gets metabolized, here if 30 mg gets metabolized by the liver 50 mg reaches the systemic circulation in the unchanged from. But Bioavailability is expressed in mg it has to be expressed in fraction. So Bioavailability is basically the fraction of unchanged from of the drug that reaches the systemic circulation following administration by any route.
As the drug given by intravenous route reaches directly into the systemic circulation. So the Bioavailability of drug given i.v is 100 %. % Bioavailability can be calculated as- Area under the curve (AUC oral)/ (AUC i.v) *100.
Bioavailability depends on both the rate and extent of absorption.
Rate of absorption depends on- site of adminstration and the drug formulation.
Extent (amount) of absorption depends on- route of drug administration
Factors affecting absorption and Bioavailability-
Pharmaceutical and pharmacological factors:
Pharmaceutical factors include- particle size, crystal from, salt form, water of hydration, Nature of excipients and adjuvants, degree of ionisation.
Pharmacological factors- gastric emptying & g.i mobility, g.i diseases, food and other substances, first-pass effect, Drug-drug interaction, pharmacogenetics, miscellaneous factors like route of administration, area of absorbing surface, state of circulation at site of absorption.
Bioavailability & Bioequivalence ppt, Objectives, Improving bioavailability, Assessment of bioavailability, Urinary excretion studies, Blood serum studies, in vitro drug dissolution testing, need for dissolution testing, in vitro drug dissolution testing models, Bioequivalence, Therapeutic equivalence, Types of bioequivalence studies, Pharmacokinetic studies, Methods to enhance dissolution rate.
Bioavailability & Bioequivalence ppt, Objectives, Improving bioavailability, Assessment of bioavailability, Urinary excretion studies, Blood serum studies, in vitro drug dissolution testing, need for dissolution testing, in vitro drug dissolution testing models, Bioequivalence, Therapeutic equivalence, Types of bioequivalence studies, Pharmacokinetic studies, Methods to enhance dissolution rate.
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).
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
A brief description on drug and food interactions, different mechanisms,effect of food-drug interactions on pharmacokinetic systems (ADME), Management of food-drug interactions
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
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.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
1.0.bioavailability, pharmacokinetics and efficacy determinationsalummkata1
Bioavailability is a measure of the rate and fraction of the initial dose of a drug that successfully reaches either; the site of action or the bodily fluid domain from which the drug’s intended targets have unimpeded access.
For majority purposes, bioavailability is defined as the fraction of the active form of a drug that reaches systemic circulation unaltered. This definition assumes 100% of the active drug that enters systemic circulation will successfully reach the target site. However, it should be appreciated that this definition is not inclusive of drugs that do not require access to systemic circulation for function (i.e., certain topical drugs). The bioavailability of these drugs is measured by different parameters discussed elsewhere.
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).
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
A brief description on drug and food interactions, different mechanisms,effect of food-drug interactions on pharmacokinetic systems (ADME), Management of food-drug interactions
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
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.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
1.0.bioavailability, pharmacokinetics and efficacy determinationsalummkata1
Bioavailability is a measure of the rate and fraction of the initial dose of a drug that successfully reaches either; the site of action or the bodily fluid domain from which the drug’s intended targets have unimpeded access.
For majority purposes, bioavailability is defined as the fraction of the active form of a drug that reaches systemic circulation unaltered. This definition assumes 100% of the active drug that enters systemic circulation will successfully reach the target site. However, it should be appreciated that this definition is not inclusive of drugs that do not require access to systemic circulation for function (i.e., certain topical drugs). The bioavailability of these drugs is measured by different parameters discussed elsewhere.
Dosage form design - Biopharmaceutical considerationAniruddha Roy
Dosage form design - Biopharmaceutical consideration: Understanding how physicochemical characteristics of a drug and formulation component affect bioactivity
The extent and rate at which its active moiety is delivered from pharmaceutical form and becomes available in the systemic circulation
Two related drugs are bioequivalent if they show comparable bioavailability and similar times to achieve peak blood concentrations.
The therapeutic index of a drug is the ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response in a population of individuals:
Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.
Absorption, Bioavailability and Bioequivalance.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Explain factor affecting drug absorption, bioavailability and bioequivalence.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
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.
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!
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
3. BIOAVAILABILITY
• 100% absorption not possible due to certain
factors that affect drug absorption.
• Liver- highly saturated with enzymes so it
does not allow drug to pass freely without
metabolizing certain amount of drug.
4. • Bioavailability is never expressed in mg.
• It is always expressed as Fraction (F)
–Here, 100 mg drug was given orally
– 50 mg (unchanged form) reached systemic circulation
– Bioavailability =
𝟓𝟎
𝟏𝟎𝟎
= 0.5
• Thus, bioavailability is fraction of unchanged drug reaching the
systemic circulation following administration by any route.
BIOAVAILABILITY =
𝐐𝐔𝐀𝐍𝐓𝐈𝐓𝐘 𝐎𝐅 𝐃𝐑𝐔𝐆 𝐑𝐄𝐀𝐂𝐇𝐈𝐍𝐆 𝐒𝐘𝐒𝐓𝐄𝐌𝐈𝐂 𝐂𝐈𝐑𝐂𝐔𝐋𝐀𝐓𝐈𝐎𝐍
𝐐𝐔𝐀𝐍𝐓𝐈𝐓𝐘 𝐎𝐅 𝐃𝐑𝐔𝐆 𝐀𝐃𝐌𝐈𝐍𝐈𝐒𝐓𝐄𝐑𝐄𝐃
Where, 0 < F 1
5. DEFINITION:
• Bioavailability is defined as “the rate and the extent to which the
active concentration of the drug is available at the desired site of
action (or bloodstream)” [as per US Food and Drug Administration].
• BIOAVAILABILITY is an absolute term which requires measurement
of both the true rate and total amount (extent) of the drug that reaches
the systemic circulation from an administered dosage form.
• EQUIVALENCE is a relative term which means a comparison of 2
different brand products of the same drug with a set of established
standards.
6. • The rate of absorption is determined by:
i. The site of administration: Fastest to slowest
ii. The drug formulation: Decreasing order
Rate of Absorption:
Intravenous
(i.v)
Sublingual Rectal Oral
Solution Suspension Capsule Tablet
Coated
tablet
7. • For drug administered i.v- Bioavailability is 100 %
• For drugs administered i.m / s.c- Close to 100%
• But for drugs administered orally: Bioavailability is < 100%.
(due to lack of absorption from the gut).
Extent (amount) of absorption:
TOO HYDROPHILIC DRUGS
(Atenolol)
cannot cross lipid cell
membrane
TOO LIPOPHILIC DRUGS
(Acyclovir)
Cannot cross water layer
adjacent to the cell
8. • Both rate of absorption and extent of input can influence the clinical effectiveness
of a drug.
• Blood concentration-time curves, shows that the changes in the rate of absorption
and extent of bioavailability can influence both the duration of action and the
effectiveness of the same total dose of the drug administered in 3 different
formulations.
9. MEASUREMENT OF BIOAVAILABILITY:
% BIOAVAILABILITY (Fab) =
𝐀𝐑𝐄𝐀 𝐔𝐍𝐃𝐄𝐑 𝐓𝐇𝐄 𝐂𝐔𝐑𝐕𝐄 (AUCoral)
𝐀𝐑𝐄𝐀 𝐔𝐍𝐃𝐄𝐑 𝐓𝐇𝐄 𝐂𝐔𝐑𝐕𝐄 (AUC𝐢
.
𝐯
)
x 100
• To calculate bioavailability: drug is given by oral and i.v route to the same person.
• Compare the bioavailability of the active drug in systemic circulation following non-
invasive administration with the same drug following intravenous administration
10. a. Peak plasma concentration (Cmax)
b. Time to attain the peak plasma concentration (tmax)
c. The area under the curve (AUC) of plasma
concentration vs time curve (till plasma
concentration has fallen to 10% of the peak value.
simple indicators for
the rate of absorption.
AUC denotes the total amount of
drug absorbed into the circulation
during a specified period.
• From plasma concentration-time curves, thus obtained 3 imp characteristics are noted and
compared:
For the product to be
considered bioequivalent-
• Cmax , tmax & AUC should
be same
11. Methods to calculate AUC:
1. Planimeter: An instrument for mechanically measuring the area of
plane figures.
2. Cut and Weigh method: To cut out the area under curve on
rectilinear graph paper and weigh it on an analytical balance.
3. Mathematical: Using Trapezoid rule.
• Measurement of AUC is a better index of bioavailability for drugs to
be given for a longer period because here the total drug absorbed
becomes more crucial than the peak concentration achieved/ the time
required to achieve the peak concentration.
12. Factors influencing absorption and
bioavailability:
Pharmaceutical
Factors
Particle
Size
Salt Form
Crystal
Form
Water of
Hydration
Nature of
Excipients
and
Adjuvants
Degree of
Ionization
Pharmacological
Factors
Gastric
Emptying and
Gastrointestinal
motility
Gastrointestinal
Disease
Food and Other
Substances
First-Pass
Effect
Drug-Drug
Interactions
Pharmacogenetic
Factors
Miscellaneous
Factors.
13. Pharmaceutical Factors:
• On Oral Administration, 2 processes precede the actual absorption
process- i) Disintegration & ii) Dissolution
14. o Particle Size:
• Particle size
1
surface area
Dissolution rate surface area
Poorly soluble drugs
Microfined
(Microfined Aspirin)
Facilitate absorption
Anthelminthic drugs
Particle size is increased
Reduce its absorption
Particle size
has no consequence on
Freely water-soluble drugs.
No need to reduce the
particle size
e.g. PARACETAMOL
15. oCrystal Form:
• Absorption rate and bioavailability of a drug depends on its crystalline form.
Amorphous forms
Dissolves better than the crystalline forms,
As no energy is required to break the
crystalline lattice
Bioavailability- Increased
e.g. Amorphous chloramphenicol palmitate,
Amorphous novobiocin
16. oSalt Form:
• A dissolution rate of a particular salt is usually different from that of the parent
compound.
Salt form of
weakly acidic/
basic drugs
Improves the
solubility and
dissolution rate
Which
increases the
absorption
BETTER
BIOAVAILABILITY
THAN
Tolbutamide
&
Phenytoin
(Free drug)
E.g. Tolbutamide Sodium
&
Phenytoin Sodium
(Salt form)
17. oWater of Hydration:
• Many drugs can associate with water to produce crystalline forms called the
hydrates.
Anhydrous forms of
(Caffeine, theophylline and ampicillin)
Faster dissolution rate and
better bioavailability
(than hydrous form)
If water molecules are already
present in a crystal structure,
the tendency of the crystal to
attract additional water and
initiate dissolution process is
reduced, compared to
anhydrous form
19. o Nature of Excipients and Adjuvants:
e.g. PHENYTOIN TOXICITY-
In epileptic patients (1968)
where in DILANTIN SODIUM CAPSULE-
Calcium sulphate was replaced with Lactose.
• Nature of excipients have
tremendous effect on bioavailability
of Drugs like-
• Phenytoin, Digoxin, Levodopa,
warfarin, etc.
20. Pharmacological Factors:
o Gastric emptying and gastrointestinal motility:
• Factors that accelerate gastric emptying increases the bioavailability because, the
drug is exposed to larger surface area of small intestine early.
Gastric emptying is
promoted by
•Fasting
•Anxiety
•Gastrokinetic- Metoclopramide
Increases drug absorption
Gastric emptying is
retarded by
Fatty diet
Anticholinergic drugs
Decreases drug absorption
Increased peristaltic
activity
Diarrhea
Decreases drug absorption
21. oGastrointestinal disease:
• Pathological factors that affect drug absorption:
– In Coeliac disease (malabsorption of fats):
Amoxycillin and pivampicillin: show decreased absorption.
Cephalexin: show increased absorption.
Ampicillin: no change.
– In Crohn’s disease (chronic inflammation of ileum):
There is a disproportionate absorption of individual components from:
cotrimoxazole
Absorption of Trimethoprim: decreased.
while Sulfamethoxazole: increased.
– In Gastroenteritis: decreased absorption of drugs if given orally.
22. o Food and other substances:
• But both the rate and extent of absorption of certain antibiotics e.g.
Rifampicin: is reduced after meals.
• Absorption of Tetracycline: reduced if taken with milk or milk products.
(forms poorly absorbed complexes with the calcium ions).
• Vitamin C: keeps Iron in ferrous form and increases its bioavailability.
• Absorption of Anti-fungal drugs (Griseofulvin): enhanced by absorption of
drugs with Fatty diet.
Empty stomach
Favors g.i absorption
Ingestion of food
Reduces rate of
absorption (not extent)
23. o First-pass effect:
• All drugs taken orally, first pass through GIT wall and then through Portal system before
reaching systemic circulation.
• A drug can be metabolized in the gut wall (e.g. CYP3A4- enzyme system- substrate for P-gp) or
in the portal circulation before reaching the systemic circulation.
• LIVER > Intestine.
• Net result: decreased bioavailability and diminished therapeutic response.
• Bioavailability of L-dopa, morphine, nitroglycerin, isosorbide dinitrate and
propranolol/labetalol is less, if given orally- due to significant first-pass effect
25. o Pharmacogenetic factors:
• Large differences in bioavailability often exist among humans due to
pharmacogenetic reasons.
• Show Increased bioavailability
Slow acetylators of
Isoniazid
(American Whites)
• Show Reduced bioavailability
Fast acetylators of
Isoniazid
(Japanese, Chinese)
Isoniazid Induced
Neurotoxicity
26. oMiscellaneous factors:
• Route of administration:
Parenteral > Rectal > Oral >
Topical.
• Area of absorbing surface:
Drugs better absorbed from small
intestine than from the stomach because
of the larger surface area of the small
intestine.
• State of circulation at the site of absorption
(in shock- where tissue perfusion gets
decreased)
Larger surface
area
Better
absorbed
27. • When 2 drugs- Drug A and Drug B are said to be bioequivalent?
• E.g., Drug company X- designs a new drug (BRANDED DRUG)
Patent for suppose-20 years. (no other company can copy this drug)
once patency expires, now any other company can legally copy this drug
(GENERIC DRUG)
But, needs approval by FDA- (asks for bioequivalence certificate)
i.e., if compound produced by A,B… companies is equivalent to compound produced by X.
i.e., It has to prove that Amount as well as rate of is similar.
• Bioequivalence: 2 pharmaceutically equivalent compound with similar rate and extent of
absorption.
• Bioequivalence is required for approval of generic drug.
• Range: normal acceptable range- 20-25 %
Needs Research,
Investments, trials
costly
No investments cheap
BIOEQUIVALENCE
28. Definition:
• EQUIVALENCE is a relative term which means a comparison of two
different brand products of a same drug with a state of established
standards.
• If 2 or more similar dosage forms of the same drug reaches the blood
circulation at the same relative rate and extent, these are called
BIOEQUIVALENT preparation of the generic drugs.
• Difference in the bioavailability is usually seen with oral dosage forms,
because bioavailability of any drug given i.v- 100%. (i.m & s.c close to
100%).
• Difference of < 25% in bioavailability among several drug formulations of
one drug will usually have no significant effect on clinical outcome, hence
such formulations can be called BIOEQUIVALENT
29. Types of Equivalence:
Chemical Equivalence:
If two or more dosage forms of the same drug contain the same labeled quantities
of the drug as specified in pharmacopoeia, these are chemical equivalent drugs.
2 Brands of a drug
May be chemically equivalent
But may not be bioequivalent
31. Therapeutic Equivalence:
If 2 brand products of 1 drug provide an “identical in vivo pharmacological
response” as measured by control of symptoms or a disease and safety profile they
can be considered therapeutically Equivalent.
They may or may not be
Pharmacokinetically equivalent
32. Clinical Equivalence:
If one structurally different drug can provide the same clinical response as another
mechanically related drug, they exhibit clinical equivalence.
33. References:
• Goodman L.S, Goodman & Gilman’s Pharmacological Basics of
Therapeutics, 13th edition, New York; New Delhi, Tata McGraw-Hill
Education, 2017.
• Katzung B.G, Basic and Clinical Pharmacology, 14th edition, New
York; New Delhi, Tata McGraw-Hill Education, 2017.
• Tripathi K.D., Essentials of Medicine Pharmacology 8th edition, New
Delhi, Jaypee Brothers Publications, 2019.
• Sharma H.L, Principles of Pharmacology, 3rd edition, New Delhi,
Paras Medical Publisher, 2018.