CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy.
Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacturing process of the drug product.
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy.
Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacturing process of the drug product.
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
introduction
mechanisms of protein drug binding
binding of drugs
binding of drugs to blood components
determination of protein drug binding
factors affecting
significance
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
introduction
mechanisms of protein drug binding
binding of drugs
binding of drugs to blood components
determination of protein drug binding
factors affecting
significance
Transporter superfamilies in the human genomeAkash Agnihotri
Transporter superfamilies in the human genome.
This includes 2 main families of transporters- SCL and ABC superfamily and their functions, locations, and sub-classification with their related disorders and drug interactions.
Also,
Transporters in pharmacokinetics
Movement of drug across cellular membrane
SLC Gene Nomenclature System
Solute Carrier Proteins (SLCs)
SLC transporters and diseases
SLC types of transporters- OAT Family, OAT Family (with example)
ABC Transporter Nomenclature System
Human ABC Superfamily
Tissue Distribution of Drug-Related ABC Transporters
ABC transporters form barriers
ABC Transporters in Drug Absorption and Elimination
A brief presentation about the transport of drugs across the cell membrane including the many mechanisms and various transporters and a brief overview of the ABC and SLC superfamily of transporters.
primary and secondary active transport difference,Computer aided drug design P glycoprotein transport,bcrp,nt,Abst,oATP,oct,BBB choline transporter,hpepti
metabolism of xenobiotis, drugs, medicine, carcinogen generation by enzymes like cyt p450 mono oxigenases, prostaglandin synthase ect. alcohol metabolism, toxin metabolism, definition of genobiotics, biotransformation, detoxification. effects on health
Introduction to drug metabolism case studies for its impacts on drug discover...SAPA-GP
2014/10/02 SAPA-GP Webinar:
Introduction to drug metabolism case studies for its impacts on drug discovery and development
Zhoupeng Zhang
Dept of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism
Merck Research Laboratories
Sino-American Pharmaceutical Professionals Association (SAPA)
– A lecture for Medicinal Chemists
(October 2, 2014)
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
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.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
A Strategic Approach: GenAI in EducationPeter Windle
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.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
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
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.
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.
2. Introduction
• Drug transporters will effect the nature of the
drug and its effects.
• Uptake – The action of taking up
• Efflux –the flowing out of a particular particle.
• Uptake and efflux transporters determine
plasma and tissue concentrations of a broad
variety of drugs.
4. • Blood-brain barrier or the maternal-fetal
barrier, have been shown to protect
sensitive tissues from potentially toxic
compounds.
• Inhibition or induction of drug
transporters by coadministered drugs can
alter pharmacokinetics and
pharmacodynamics of the victim drugs.
• Each transporter has a specific pattern of
tissue expression.
6. • Efflux transporters such as P-glycoprotein , the
breast cancer resistance protein , and the
multidrug resistance protein are localized to
the apical membrane of enterocytes [a cell of
the intestinal lining ], thereby limiting
bioavailability of orally administered
substrates.
• After absorption and passage through the
portal vein, drugs reach the basolateral
[ situated below and toward the side ]
membrane of hepatocytes
7. • Inhibition of these efflux
transporters by concomitantly
administered drugs results in an
increased bioavailability of the
victim drug.
• Whereas induction of these
intestinal efflux transporters
reduces bioavailability of drug
substrates.
8. • Drug transporters also play a major role for
drug secretion from the proximal tubular cells
of the kidney into urine.
• uptake and efflux transporters for organic
anions are also expressed in the kidney.
Inhibition of these processes by concomitantly
administered drugs leads to a reduced renal
clearance of the victim drug.
10. Intestinal lumen
• The human OATP family consists of 11 members
grouped into six subfamilies based on their amino
acid sequence similarities.
• From these OATP proteins, to this day four have
been identified as being important for drug
therapy.
• OATP1A2 reported to be expressed in the
intestinal epithelium , the renal epithelium, and
highly expressed in brain capillary endothelial
cells
11. Transporters expressed in enterocytes of the human intestinal
epithelium. Uptake transporters discussed in this review are colored in
red, export pumps in blue.
12. Hepatocytes
• OATP1B1 and OATP1B3 , exclusively
expressed in human hepatocytes.
• OATP2B1 the OATP family member being
expressed in almost all tissues.
• OATP1B3 seems to be expressed in colon
polyps, colon cancer and in pancreatic
adenocarcinoma.
13. • these play an important role for drug
disposition.
• An important drug class with compounds
being transported by OATP1A2, OATP1B1,
OATP1B3, and OATP2B1 are HMG-CoA
reductase inhibitors (statins).
• Pitavastatin has been identified as substrate
for all four OATPs .
14. • several other drugs have been identified as
substrates for these OATP family members, including
antibiotics, chemotherapeutic agents, antihistaminic
drugs, and diuretics.
• The OAT/OCT Family of
organocation/anion/zwitterion transporters consists
of 23 human members, including the cation
transporters OCTs, the anion transporters OATs.
• The OCT1 protein exhibits a broad tissue distribution
with a high expression in liver and weaker expression
in some other tissues such as spleen and lung.
15. • Drugs transported by or inhibiting
all three OCTs in vitro include
anesthetic drugs -ketamine and
cocaine, b-blockers -propranolol
antidepressants-Citalopram and
oral antidiabetic drugs -
metformin .
16. Transporters expressed in human hepatocytes. Uptake transporters
discussed in this review are colored in red, export proteins in blue.
17. Brain intestinal space
• The anion transporters OAT1 is expressed in
different tissues with the highest expression in
kidney and located there in the basolateral
membrane of proximal tubule cells .
• In addition, mRNA transcripts of OAT1 have been
detected in the brain [cerebellum, hippocampus,
and hypothalamus and the choroid plexus . OAT2
is highly expressed in human liver and to a lower
extent also in the kidney with the same
localization as the OAT1 protein.
18. Transporters expressed in human brain capillary endothelial
cells. Uptake transporters discussed in this review are colored in red,
export proteins in blue.
20. • The human multidrug resistance/transporters
of antigen presentation (MDR/TAP) family
consists of 11 different ABC transporters
including the peptide transporters.
• TAP1 and TAP2 are the phospholipid
translocator .
• The drug export pump, and the bile salt
export pump are important for drug
disposition
21. • P-gp is the most studied export pump
mediating the transport of drugs and drug
conjugates from the intracellular to the
extracellular space.
• It is expressed in several tissues including
intestine, kidney, liver, brain and placenta.
• P-gp is expressed in the apical membrane of
the entire intestine from duodenum to rectum
22. • P-gp is also important for the blood-brain barrier
as a defense mechanism against the penetration
of toxins and drugs into the central nervous
system.
• P-gp has a very wide substrate spectrum
mediating the export of a variety of drugs from
different drug classes. Substrates include
anticancer drugs (e.g., docetaxel, etoposide,
vincristine), immunosuppressants [e.g.,
cyclosporine (CsA), tacrolimus], antibiotics (e.g.,
macrolides), statins (e.g., atorvastatin, lovastatin),
cardiac drugs (e.g., digoxin, digitoxin), and b-
blockers e.g., carvedilol;
23. • P-gp is an important determinant of
pharmacokinetics and an important mediator
of transporter-mediated drug-drug
interactions.
• The second MDR1/TAP family member, which
is in particular important for drug side effects
via inhibition of this transporter, is the bile salt
export pump BSEP.
• BSEP shows the highest expression in liver and
is located in the canalicular membrane of
hepatocytes.
24. • The apically localized export pump MRP2 seems
to be the most important member of this family
for drug disposition.
• MRP2 represents an apically localized export
pump of the MRP family and is highly expressed
in liver, kidney, small intestine , gall bladder, and
placenta.
• The exclusively apical localization is in line with its
role for the excretion of many phase II
metabolites of drugs and endogenous
compounds into bile, urine, and the intestinal
lumen.
25. • Breast cancer resistance protein (BCRP) is a member of
the ABCG family of ABC transporters. This is so-called
half-size ABC transporter is expressed in different
tissues including intestine, liver, kidney, brain, in
addition in testis and placenta.
• Substrates include antivirals e.g., acyclovir, statins e.g.,
pravastatin and rosuvastatin , anticancer drugs e.g.,
topotecan , antibiotics e.g., ciprofloxacin and ofloxacin,
as well as diclofenac , sulfasalazine , and cimetidine.
• Furthermore, endogenous substances and metabolites
such as vitamin K3 , estrone-3-sulfate,
dehydroepiandrosterone sulfate, and uric acid have
been shown to be transported by BCRP.
26. • Substances that inhibit BCRP-mediated
export in vitro without being transported
itself include cyclosporine, omeprazole
and pantoprazole,saquinavir, and
tacrolimus.
• MATE1 is expressed in both liver and
kidney, MATE2-K is highly expressed in
kidney and to lower levels also in colon
and testis.