This document provides an introduction to the concepts of pharmacokinetics. It defines pharmacokinetics as the mathematical description of drug behavior in the human body, including absorption, distribution, metabolism and excretion of drugs. The objectives are to teach students how to analyze pharmacokinetic data using graphs and calculations, and apply the principles of pharmacokinetics to predict drug performance and optimize therapeutic outcomes. Key concepts covered include volume of distribution, bioavailability, clearance, and the relationships between drug dose, concentration and pharmacological response over time.
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.
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.
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
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
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
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
General Pharmacology Lecture Slides on Bioavailability and Bioequivalence by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College
Pharmacokinetics (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.
This is part two of the diabetes presentation aimed for pharmacists and allied health professional who are interested in tailoring special pharmaceutical care plans for diabetic patients.
Many have troubles choosing the proper insulin type and dosing for their patients.. Here is a quick presentation that introduce you to different studies in that matter.
This presentation is intended for healthcare prfessionals
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Embracing GenAI - A Strategic ImperativePeter 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.
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!
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
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
Home assignment II on Spectroscopy 2024 Answers.pdf
Pharmacokinetics: Lecture One
1. Introduction
To Pharmacokinetics
Pharmacokinetics A Mathematical Tool
Anas Bahnassi PhD RPh
2. Lecture Objectives
After completing this lecture, the student will be able
to:
1. Given patient data of the following types, the student will be able to
properly construct a graph and compute the slope using linear
regression: response (R) vs. concentration (C), response (R) vs. time
(T), concentration (C) vs. time (T)
2. Given any two of the above data sets, the student will be able to
compute the slope of the third by linear regression.
3. Give response vs. time and response versus concentration data, the
student will be able to compute the terminal (elimination) rate
constant and half life of the drug.
3. What is Pharmacokinetics?
The mathematical description
of drug behavior inside the human body
It is the study of factors affecting
the absorption, distribution,
metabolism and excretion of drug
As well as the quantitative description
of how these processes affect the
time course and intensity of response.
4. What is Pharmacokinetics?
This powerful mathematical tool is used
to study the drug’s
• Fate in normal and
pathophysiological conditions
• Distribution / location /penetration
• Clearance / organs
• Conc vs. response
• Bioavailability
• It compares dosage forms and
different drug brands
• It quantitatively evaluate the
magnitude of drug interactions
• It provides the basics to make clinical
predictions
5. What is Biopharmaceutics?
How the pharmaceutical formulation
variables affect drug availability and performance
(absorption)
in vivo
The use of these information helps optimizing
therapeutic outcomes of drug products
6. Distribution
Elimination
Metabolites
• IV Medication
• PO in
Circulation
• IM
• MDI Dosage
Regimen
Concentration
Response
Route of
Administration
• Pharmacological
• Adverse
Effect
The Pharmacokinetic Process
7. The Pharmacological Response
Drug must get into
The occupation theory blood
The intensity of a pharmacological and blood is in
response (E) is proportional to the contact
concentration of a reversible drug- with receptor.
receptor complex
where E is the intensity of the
������ ������������������������ pharmacological response, Emax is the
������ = maximum attainable value of , [D] is the
������������ ������ molar concentration of free drug at the
active complex and KR is the dissociation
constant of the drug-receptor complex.
8. m:slope Response vs. Drug
E=m.lnX+b
Concentration
X:dose = C.V V:volume
of
Emax
distribution
9. The Relationship Between The Administered
Dose and The Amount of the Drug in The Body
• The Fraction of the drug reaches the systemic
circulation is the amount available to elicit
pharmacologic effect.
• For iv administration, the amount of drug
reaches the general circulation is equal to the
dose administered.
∞
������������������������ = ������0 = (������������������)0 ������������
(AUC)∞0 is the area under curve of plasma drug concentration versus time (AUC) from
time zero to time infinity
K is the first-order elimination rate constant
V (or Vd) is the drug’s volume of distribution. 9
10. Volume of Distribution
“The apparent volume into which a given mass
of drug would need to be diluted in order to give
the observed concentration.”
������
������ =
������
Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009
Anas Bahnassi PhD 2011 10
11. The Relationship Between The
Administered Dose and The Amount of the
Drug in The Body
For the extravascular route, the amount of
drug that reaches general circulation is the
product of the bioavailable fraction (F) and
the dose administered.
∞
������. ������������������������ = ������������0 = (������������������)0 ������������
Anas Bahnassi PhD 2011 11
12. Min. Toxic Conc.
Min. Effective Conc.
Previous equations suggest that we must know or determine
all the parameters (i.e. AUC, 0 , K, V, F) for a given drug;
therefore, it is important to know the concentration of a drug
in blood (plasma or serum) and/or the amount (mass) of drug
removed in urine (excretion data).
Anas Bahnassi PhD 2011 12
13. Onset of Action:
The time at which the administered drug reaches the therapeutic range
and begins to produce effect.
Therapeutic Range:
The plasma or serum concentration range within which the drug is
likely to produce the therapeutic activity or effect
Duration of Action:
The time span from the beginning of the onset of action up to
termination of action
Termination of Action:
The time at which the drug concentration in plasma falls below the
minimum effective concentration
Anas Bahnassi PhD 2011 13
15. Sites of Drug Administration
1. There is no absorption
phase.
Intra- 2. There is immediate
Intravascular venous onset of action.
3. The entire administered
Routes dose is available to
Intra- produce pharmacological
arterial effects.
4. This route is used more
often in life-threatening
situations.
5. Adverse reactions are
difficult to reverse or
control; accuracy in
calculations and
administration of drug
Anas Bahnassi PhD 2011 dose, therefore, are very
15
critical.
16. Sites of Drug Administration
Oral
Inhalation
Intra-
mascular
Extra-
vascular Sub-
Rectal cutaneous
Trans- Sub-
dermal lingual
Anas Bahnassi PhD 2011 16
17. Important Features of
Extravascular Routes
1. An absorption phase is present.
2. The onset of action is determined by factors such as formulation and
type of dosage form, route of administration, physicochemical properties
of drugs and other physiological variables.
3. The entire administered dose of a drug may not always reach the
general circulation (i.e. incomplete absorption).
Anas Bahnassi PhD 2011 17
18. Review of the ADME Process
• The process by which a drug proceeds from
Absorption the site of administration to the site of
measurement
• the process of reversible transfer of drug to
Distribution and from the site of measurement
• the process of a conversion of one chemical
Metabolism species to another chemical species
• The irreversible loss of drug from the site of
Elimination measurement. It may occur by metabolism
or excretion.
Anas Bahnassi PhD 2011 18
19. Excretion Disposition
The irreversible loss of Once a drug is in the systemic,
a drug in a chemically it is distributed simultaneously
unchanged or unaltered to all tissues including the organ
form. responsible for its elimination.
Anas Bahnassi PhD 2011 19
20. Pharmacokinetic Models
The change in drug’s concentration after administration can be described
using certain equations mostly exponential. This suggests that ADME
processes follow a first order process and therefore drug transport is
mediated through passive diffusion mechanism. This means that there is a
direct relationship between the plasma concentration of the drug and the
amount eliminated in the urine and the original administered dose. This
identifies the term Linear Pharmacokinetics.
Anas Bahnassi PhD 2011 20
21. Compartment Concept in PK
• It is necessary to describe the pharmacokinetic
parameters adequately and accurately.
• The selection of the compartment model
depends solely on the distribution
characteristics of the drug administered.
• The corresponding equation depends on the
compartment model and the route of
administration.
Anas Bahnassi PhD 2011 21
22. The model selection process is highly
dependent upon the following factors.
1. The frequency at which plasma samples are collected. It is
highly recommended that plasma samples are collected as
early as possible, particularly for first couple of hours,
following the administration of the dose of a drug.
2. The sensitivity of the procedure employed to analyze drug
concentration in plasma samples. (Since inflections of the
plasma concentration versus time curve in the low
concentration regions may not be detected when using assays
with poor sensitivity, the use of a more sensitive analytical
procedure will increase the probability of choosing the correct
compartment model.)
3. The physicochemical properties (e.g. the lipophilicity)of a
drug.
Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009
Anas Bahnassi PhD 2011 22
24. IV Bolus Dose - One
Compartment
Considering the body to
behave as a single
compartment. In order to
simplify the mathematics it
is often possible to assume
that a drug given by rapid
intravenous injection, a
bolus, is rapidly mixed. This
figure represents the
uniformly mixed drug very
shortly after administration.
Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142
Anas Bahnassi PhD 2011 24
25. IV Bolus Dose - One
Compartment
������ = ������0 ������ −������������ = ������������ −������������ 1
������������������ = ������������������ − ������������ (2)
E=m.lnX+b
������ − ������ ������0 − ������
= ������������ (3)
������ ������
E=E0-Rt
Basic Pharmacokinetics REV. 99.4.25 3-4 1996-1999 Michael C. Makoid
Niazi, S. 1979 Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, p142
Anas Bahnassi PhD 2011 25
26. IV Bolus Two
Compartment Model
Often a one compartment model is not sufficient to represent the
pharmacokinetics of a drug. A two compartment model often has
wider application. Here we consider the body is a central
compartment with rapid mixing and a peripheral compartment
with slower distribution.
The central compartment
is uniformly mixed very
shortly after drug
administration, whereas
it takes some time for the
peripheral compartment
to reach a pseudo
equilibrium.
Niazi, S. 1979 Textbook of Biopharmaceutics and
Clinical Pharmacokinetics, Appleton-Century-
Crofts, New York, p175l.;l
Anas Bahnassi PhD 2011 26
30. A basic model for absorption and
Disposition
The model is based on mass
balance considerations:
At any time t, for the
1. The amount (e.g. mg) of
extravascular route:
unchanged drug and/or
F(Dose) = absorbable amount at
metabolite(s) can be measured in
the absorption site + amount in the
urine.
body + cumulative amount
2. Drug and metabolite(s) in the
metabolized + cumulative amount
body (blood, plasma or serum)
excreted unchanged
are measured in concentration
units (e.g. μgmL-1).
For the intravascular route:
3. Direct measurement of drug at
Dose = amount in the body +
the site of administration is
amount metabolized + cumulative
impractical; however, it can be
amount excreted unchanged:
assessed indirectly.
Anas Bahnassi PhD 2011 30
31. Characteristics of One
Compartment Model
1. Equilibrium between drug concentrations in
different tissues or organs is obtained rapidly
(virtually instantaneously), following drug input.
Therefore, a distinction between distribution and
elimination phases is not possible.
2. The amount (mass) of drug distributed in different
tissues may be different.
3. Following equilibrium, changes in drug concentra-
tion in blood (which can be sampled) reflect
changes in concentration of drug in other tissues
(which cannot be sampled).
Anas Bahnassi PhD 2011 31
32. Drug Concentration versus Time
From a graph such as this we can see the relationship between drug
concentration and drug effect. If a drug has to reach an effective
concentration at a receptor site this will be reflected as a required
blood concentration.
Barr, W.H. 1968 Principles of Anas Bahnassi PhD 2011 32
biopharmaceutics, Amer. J. Pharm. Ed., 32,
958
33. Drug Product Performance
Parameters
The figure shows
some of the bio-
pharmaceutic
parameters
which can be
used to measure
drug product
performance.
Later in the
semester we will
use the trap-
ezoidal method
Dittert, L.W. and DiSanto, A.R. 1973 The bioavailability of drug
of calculating
products, J. Amer. Pharm. Assoc., NS13, 421-432 AUC.
Anas Bahnassi PhD 2011 33
34. Rate Processes
After administration, the drug
is subject to a number of
processes (ADME) whose rates
control the concentration of
drug in the elusive region
known as ‘‘site of action.’’
These processes affect the onset
of action, as well as the duration
and intensity of
pharmacological response.
Anas Bahnassi PhD 2011 34
35. Zero-order Process
Applications of zero-
order processes include
administration of a
drug as an intravenous
infusion, formulation
and administration of a
drug through
controlled release
dosage forms and
administration of drugs
through trans-dermal
drug delivery systems.
Anas Bahnassi PhD 2011 35
Rectilinear Paper
40. Comparison of Zero & First order
processes
Term Zero order First order
-dx/dt = K0 Rate remains KX Rate changes over time
constant
Rate =K0 =K
constant unit = mgh-1 unit=h-1
X X=X0-Kt lnX=lnX0-Kt or
logX=logX0-kt/2.303
Anas Bahnassi PhD 2011 40