Bioavailability refers to the amount of drug that reaches systemic circulation in an unchanged form following administration. It is measured as the area under the plasma concentration-time curve (AUC) following oral administration divided by the AUC following intravenous administration. Factors that affect bioavailability include absorption from the site of administration, first-pass metabolism in the liver and gut, chemical instability in the GI tract, solubility of the drug, and pharmaceutical formulation. Drugs with a high extraction ratio undergo significant first-pass metabolism, reducing their oral bioavailability. Alternative routes of administration can be used to avoid first-pass metabolism. Bioequivalence refers to different formulations having the same bioavailability and absorption rates, while bioinequivalence means they
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
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
Bioavailability & Bioequivalence Studies
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Sub :- Research Methodology
M.Phrmacy Semister 1
Savitribai Phule Pune University
Bioavailability:
Bioavailability is defined as a measure, of the rate and amount of drug, which reaches the systemic circulation unchanged following the administration of a dosage form.
Absolute bioavailability:
When systemic availability of a drug administered orally
is determined in comparison to its I.V. administration, denoted by F.
Relative bioavailability:
When systemic availability of a drug after oral administration is
Compared with that of oral standard of the same drug
( Solution or suspension ) and denoted by Fr.
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.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
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
Bioavailability & Bioequivalence Studies
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Sub :- Research Methodology
M.Phrmacy Semister 1
Savitribai Phule Pune University
Bioavailability:
Bioavailability is defined as a measure, of the rate and amount of drug, which reaches the systemic circulation unchanged following the administration of a dosage form.
Absolute bioavailability:
When systemic availability of a drug administered orally
is determined in comparison to its I.V. administration, denoted by F.
Relative bioavailability:
When systemic availability of a drug after oral administration is
Compared with that of oral standard of the same drug
( Solution or suspension ) and denoted by Fr.
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.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Ace Your NAPLEX Exam: Master Kinetics, DDI, and Pharmacogenomics in Lecture 2!Jackson Wang
https://youtu.be/C1Rb4BFugzo
Attention all NAPLEX students! Are you ready to take your studying to the next level? In this video, we dive deep into the world of Kinetics, DDI, and Pharmacogenomics. With other pharmacy students that seeks to inspire, this lecture provides insight on how to approach your NAPLEX studies with a fresh perspective. But, we want to know, what's been your biggest challenge so far while memorizing this vital information? Leave your thoughts below and let's engage in a discussion that will motivate us all. Remember, don't just study harder, study smarter. Join the conversation and elevate your NAPLEX studying game.
https://youtu.be/C1Rb4BFugzo
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.
Whenever a drug is given orally it has to go through certain pathway to reach systemic circulation.
E.g out of 100 mg drug given orally if 80 mg gets absorbed & 20 gets excreted. 80 mg of absorbed drug then reaches the liver through portal vein. Liver is highly saturated with enzymes so it doesn't allow the drug to pass freely through it without metabolizing certain amount of drug. . So if 30 mg of absorbed drug gets metabolized in the liver remaining 50 mg of drug reaches the systemic circulation in the unchanged form. But Bioavailability is never expressed in mg it is always 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.
Whenever drug is given intravenously 100% drug reaches the systemic circulation in an unchanged form. So the Bioavailability of the drug given intravenously is 100%, while that of the drug given orally is < 100%
Bioavailability of a drug depends on the rate and extent of absorption.
Rate of drug administration is determined by: site of drug administration and drug formulation.
Extent (amount) of drug absorption is determined by: route of drug administration.
Factors affecting drug absorption and Bioavailability- There are various pharmaceutical and pharmacological factors that affect the drug absorption.
FIRST PASS METABOLISM:-
The drug given orally first pass through GI wall and then reaches the liver through portal system. The drug can also be metabolized in the gut wall CYP3A4 enzyme which is a substrate for P-gp {P-glycoprotein (P-gp) is an active transporter which pumps drug out of the gut wall cells back into the gut lumen against the concentration gradient.) Normally, drug enters the intestinal lumen by passive diffusion (i.e along the concentration gradient). But P-gp causes drug efflux or drug wastage (i.e against the concentration gradient); The amount of drug that disappears contribute first pass metabolism. But first pass metabolism occur in LIVER > INTESTINE.
Some amount of drug while passing through the liver gets metabolized in the liver for the first time before reaching the systemic circulation this known as first pass metabolism.
Bioequivalence- it as comparison of 2 different brand products of a same drug.
E.g. if Drug company X designs a new drug - (BRANDED DRUG) it gets patency for suppose 20 yrs. So that no other company can legally copy this drug. But once the patency expires any other company can legally copy this drug (GENERIC DRUG) but requires approval by FDA. and FDA asks for BIOEQUIVALENCE certificate (i.e it checks if the compound produced by other company is equivalent to that of BRANDED DRUG.) It has to prove that amount as well as rate of absorption is similar. No company can copy the drug 100% as it is. therefore the acceptable range is +/- 20-25%. The drug can be chemically, pharmaceutically, Therapeutically & clinically equivalent.
Thank you
Clearance of drugs.
Elimination of drugs - sites
Review of renal physiology.
Nature of drugs & factors affecting elimination.
Drug half life
Steady state concentration & Maintenance dose.
Clearance: Volume of plasma that is cleared of drug per unit time.
Elimination rate: is mass/amount of drug that is cleared from the body.
Clearance is related with elimination by a constant proportion factor.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
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Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
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Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
2. Bioavailability
• It the fraction of drug that
reaches the systemic
circulation in a chemically
unchanged form, following
administration by any route
3. Bioavailability & route of administration
• I/V route = unity (one) or 100 %
By any other route may be less than 100 %
• I/M --- 75 to ≤100
• SC --- 75 to ≤ 100
• Oral --- 5 to ≤ 100
• Rectal --- 30 to ≤ 100
• Inhalation --- 5 to ≤ 100
• Transdermal --- 80 to ≤ 100
4.
5. How bioavailability is measured
• It is measured by determining the
plasma drug concentration versus
time curves in a group of subjects
following oral and (on separate
occasion) I/V administration.
6. How bioavailability is measured
•Bioavailability =
AUCoral/AUCintravenous
– AUC --- area under the blood concentration curve
7.
8.
9.
10. Factors affecting bioavailability
• Factors which reduce the bioavailability to < 100 %
• Reduced absorption from the site
of administration
•First pass elimination ---
Drug undergoes metabolism or
elimination prior to entering the
systemic circulation
11. Factors affecting the rate and extent of
absorption
•Nature of drug
formulation
•Chemical instability
•Solubility of the drug
13. Solubility of the drug
• Very hydrophilic drugs --- Poorly absorbed ---
unable to cross lipid rich cell membranes
• Extremely hydrophobic --- Poorly absorbed -
-- cannot gain access to the surface of the
cells
• Largely hydrophobic, yet have some
solubility in aqueous solutions --- Readily
absorbed
14. Pharmaceutical formulation and
bioavailability
• A drug is incompletely released from its
dosage form because of differences in
the pharmaceutical formulation
unrelated to the chemistry of the drug
• Particle size, salt form, enteric coating,
crystal polymorphism, compression
pressure during manufacturing,
moisture content
15. Pharmaceutical formulation and
bioavailability
• The special formulations may alter
absorption “slow release” or
“sustained-release” formulation
• “Enteric coating” prevents
breakdown of tablets by acid pH of
the stomach
16. “First-pass” effect
• “presystemic elimination” or
• “first pass elimination”
• The elimination in the intestine
and liver, which reduces the
amount of drug delivered to the
systemic circulation
17. Elimination in the intestine
• Excretion back into the intestinal lumen
• Metabolism
19. First pass hepatic metabolism
• If a drug is metabolized by the liver,
the amount of drug that reaches the
systemic circulation is decreased
• Significant biotransformation during a single
passage through the liver
• Propranolol and lidocaine
20. Extraction ratio
• The effect of first pass hepatic
elimination on bioavailability is
expressed as the extraction ration
CLliver
ER = --------------------
Q (hepatic blood flow)
21. Drugs with high extraction ratio
by the liver
• Propranolol
• Isoniazid
• Verapamil
• Morphine
• TCAs
22. Drugs that are poorly extracted
by the liver
• Warfarin
• Diazepam
• Phenytoin
• Theophyllin
• Toulbutamide and
• Chlorpropamide
23. Variation in Extraction ratio
•Marked variation in
bioavailability between
subjects because of
differences in hepatic
function and blood flow.
24. Alternative routes of administration
are used to avoid the first pass effect
• Parenteral routes --- Provides direct access to
systemic – not portal vein
• “Intra” ---Three common routes --- IV, IM, SC
• Topical --- To maximize concentration at
site of action and minimize it elsewhere
• Transdermal -- To prolong the duration of
drug absorption
25. Alternative routes of administration
are used to avoid the first pass effect
• By inhalation
• S/L absorption provides direct
access to systemic – not portal vein
• P/R
–Lower rectum --- into inferior vena
cava
–Upper rectum – to the liver
27. Bioavailability – and route of
administration
• Drugs that undergo near-complete
presystemic metabolism and thus
cannot be administered orally ---
nitroglycerine – given by sublingual
or transdermal route
28. Bioavailability – dose of the drugs
• Drugs with extensive presystemic metabolism
can still be administered by the oral route,
using much higher doses
• Verapamil – I/V – 1-5 mg, orally 40-120 mg
• Low dose aspirin --- result in exposure of
cyclooxygenase in platelets in portal vein to
the drug, but systemic sparing because of
first-pass aspirin deacylation in the liver
29. Bioequivalence / bioinequivalence
• For comparison of the bioavailability of the
“Generic equivalent of patented products”
• Different pharmaceutical
formulation of the same drug, are
given at same dose, by the same
mode and their bioavailability is
compared
31. Bioequivalence
• When different pharmaceutical
preparations have same
bioavailability and the same rate of
absorption.
• When this occurs, the plasma levels
of the two products will be super
imposable
32. Bioinequivalence
• When different pharmaceutical
preparations are given and there is
significant difference in the
bioavailability & rate of absorption
• When this occurs, the plasma levels
of the two products will not be super
imposable
33. Therapeutic equivalence
• Two similar drugs are therapeutically
equivalent if they have comparable
efficacy and safety
• Clinical effectiveness
–Maximum serum drug concentration
–Time required (after administration) to
reach peak concentration
37. Bioavailability differences between
three preparations of a drug containing the same amount
Bioavailability A = B (AAUC = BAUC)
B may not produce the therapeutic effect
38. Bioavailability differences between
three preparations of a drug containing the same amount
Bioavailability A = B (AAUC = BAUC)
B may not produce the therapeutic effect
C lower bioavailability
