This document discusses dosage regimens for drugs administered through multiple doses. It defines key concepts like maintenance dose, loading dose, and accumulation index. The loading dose is given to quickly reach the steady state concentration, while the maintenance dose is used to maintain that concentration by replacing eliminated drug. The accumulation index describes the extent of drug accumulation in the body during multiple dosing as a function of dosing interval and elimination half-life. Designing optimal dosage regimens requires considering factors like dose size, dosing frequency, and pharmacokinetic parameters.
CONCEPT OF LOADING AND MAINTAINANCE DOSE.pptxNamrataSawant19
Most drugs for chronic condition are prescribed in a dosage regimen is based on the administration of a fixed constant dose(D) at fixed regular dosing intervals(T) for long period of time.
The D & T recommended by the manufacturer is based on the effective therapeutic concentration of drug in the plasma needed to treat the chronic condition.
Primary purpose of using loading dose in therapeutic treatment is to attain steady-state concentration of the drug as quickly as possible, usually right from the start of the dosage regimen for the treatment.
CONCEPT OF LOADING AND MAINTAINANCE DOSE.pptxNamrataSawant19
Most drugs for chronic condition are prescribed in a dosage regimen is based on the administration of a fixed constant dose(D) at fixed regular dosing intervals(T) for long period of time.
The D & T recommended by the manufacturer is based on the effective therapeutic concentration of drug in the plasma needed to treat the chronic condition.
Primary purpose of using loading dose in therapeutic treatment is to attain steady-state concentration of the drug as quickly as possible, usually right from the start of the dosage regimen for the treatment.
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.
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).
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
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
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.
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).
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
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.
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.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
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
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.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
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
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.
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
3. 3
Introduction
Definition :- Dosage regimen is defined as the Manner in
which a drug is taken.
For successful therapy, design of an optimal multiple dosage
regimen is necessary.
Multiple dosage regimen:- is defined as the manner in which
the drug is administered in suitable doses by suitable route,
with sufficient frequency that insures maintenance of plasma
conc. within therapeutic window for entire period of therapy.
In designing a dosage regimen:-
• All p’kinetic parameters of the drug remain constant during the
course of therapy once the Dosage regimen is established.
• The calculations are based on one- compartment model which
can also applied for two- compartment models. β KE
Vd,ss Vd
4. 4
In Designing dosage
regimen the two major
parameters that can be
adjusted in developing a
dosage regimen are…
1) The Dose size – The qty.
of Drug administered.
Greater dose size
greater fluctuation btw
Cssmax, & Cssminand greater
chance of toxicity
2) The Dosing frequency –
The time interval
between Doses.
5. 5
Design of dosage regimen from plasma
concentration :
If the Vd and clearance or half life of the drug is known,
then dosage regimen can be design to maintain the drug
conc. in the therapeutic range.
Maximum dosing interval which ideally depends upon the
therapeutic index and elimination half life of the drug can
be expressed as :
זז max = 2.303 log ( Cupper / Clower )
KE
Where KE = 0.693/t1/2
6. 6
זז max= 3.32 t1/2 log ( Cupper / Clower )
Mostly dosing interval selected is always smaller than זז max
the maximum maintenance dose X0maxcan be expressed as
X0max= Vd ( Cupper - Clower )
F
After the convenient dosing interval זז ,, smaller thansmaller than זז max has
been selected, maintenance dose is given as :
X0 = Css,av =
Xo max
זז maxmax
זז
( Cupper / Clower )
2.303 log ( Cupper / Clower )
7. 7
Multiple dosing
For chronic diseases, there is necessity of multiple dosing
i.e. administration of drugs in number of frequencies.
On continuous steady administration of a drug, plasma
concentration will rise fast at first then more slowly and
reach a plateau, where:
Rate of administration = Rate of elimination
( steady state is achieved )
Therefore, at steady state:
Dose (Rate of Administration) = Clearance x Plasma conc.
Or
If you aim at a target plasma level and you know the
clearance, you can calculate the dose required.`
8. 8
Effect of multiple doses
If the plasma concentration prior to next dose is >0
concentration and elimination is of first order, then plasma
concentration will increase Increase in elimination rate
and eventually steady state.
– For first order elimination kinetic the time to obtain
steady state is dependent only of the half time of the drug
– The steady state concentration is determinated by dose
(D) and dose frequency
9. 9
Effects of dose and dose frequencyEffects of dose and dose frequency
Increase in doseIncrease in dose
– Increase in CIncrease in Cmeanmean
– Larger difference between CLarger difference between Cmaxmax and Cand Cminmin
– Increased risk for side effects for drugs with smallIncreased risk for side effects for drugs with small
therapeutic windowstherapeutic windows
Increase in frequencyIncrease in frequency
– Increase in CIncrease in Cmeanmean
– Larger inconvenience for patientLarger inconvenience for patient
10. 10
Loading Dose
Concept of loading dose
For drugs with long half-lives, the time to reach steady
state might be long. It takes about 5 half- lives to reach
steady state.
In a such cases the plateau can be achieved by
administering a dose that gives the desired steady- state.
Such an initial/ first dose is called as Loading dose.
XXo,o,L =L =
CCss,avss,av VVdd
FF
11. 11
When Vd is not known then loading dose may be
calculated as
The above eq. is applied when Ka >> Ke & drug is
distributed rapidly.
But in case of I.V. route the absorption is very fast
therefore , absorption phase is neglected then above eq.
XXooLL
XX00 (1 –e(1 –e –Ka–Kaזז
)) (1 – e(1 – e –Ke–Ke זז
)
11
=
XXo,o,LL
XX00
=
1 – e1 – e -Ke-Keזז
11
= R= Racac
12. 12
Maintenance Dose
After the loading dose is given the another dose (I.V) is
given to maintain the steady- state drug conc. Or plateau.
Such dose is known as maintenance dose.
i.e. maintain the response of drug by replacing drug lost
during dosing interval.
Maintenance dose = loading dose x ( 1- e -kז
)
Loading dose =
maintenance dosemaintenance dose
1 – e1 – e -K-K זז
13. 13
The ratio of loading dose
to maintenance dose
(X0L/X0) is called as dose
ratio
When ז = t1/2 the dose ratio
=2.0
When ז > t1/2 the dose ratio
< 2.0
when ז < t1/2 the dose ratio
>2.0
14. 14
Accumulation Index
In case of multiple dosage regimen (drugs are frequently
administered) in such a cases the 1st
drug conc. remaining
in a body after certain time, is added to the next dose, this
condition is known as ‘Accumulation’
The accumulation occurs because previous doses has not
been removed completely from body.
After some time the rate of absorption is equal to rate of
elimination i.e. conc. of drug in plasma approaches to a
constant value this condition is called as steady- state,
plateau/ infusion equilibrium.
16. 16
Consider the Amount of drug in the body-time profile as
shown in the Graph.
After admin of first dose X0 = 1X0
At next dosing interval when X = ½ X0, amt of drug
remaining in the body
Admin of next i.v. dose raises the body content to
X = X0+ 1
/2X0
As the amount of drug in the body rises gradually due to
Accumulation, the rate of elimination also rises
proportionally until a steady-state or Plateau is reached.
17. 17
The maximum & minimum values of X i.e. Xss,max & Xss,min
approach respective asymptotes at plateau.
Plateau Xss,min = 1X0 (amt of drug in body after first dose ) Xss,max =
2X0 ( equals twice the first dose)
Also (Xss,max- Xss,min) = X0
Xss,max / Xss,min = 2
All this applied only when ז = t1/2
18. 18
When ז < t1/2 , the degree of Accumulation is greater & vice-
versa.
Thus, the extent to which a drug accumulates in the body
during multiple dosing, is a function of dosing interval &
elimination half life & is independent of dose size.
The extent to which a drug will accumulate with any dosing
interval in the patient can be derived from information
obtained with a single dose and is given by accumulation
index Rac as:
=Rac
1
1-e -KE ז
19. 19
References
‘Applied Biopharmaceutics & Pharmacokinetics’
by Leon Shargel & Andrew B. C. Yu, 4th
Edition
‘Biopharmaceutics & Pharmacokinetics’
A Treatise, D. M. Brahmankar & Sunil B. Jaiswal
‘Clinical Pharmacokinetics, Concepts &
Application’, 3rd
Edition,
by Malcom Rowland & Thomas N. Tozer, Lea & Febiger
www.google.com