Definition of Biopharmaceutics, Application of Biopharmaceutics, Definition of Absorption, Distribution, Metabolism, Excretion, Pharmacokinetics, pharmacodynamics, Bioavailability, Bio-equivalence, Plasma Concentration Vs Time Profile, Pharmacokinetics & pharmacodynamics parameters
Muhtasari wa kitabu cha jinsi ya kutunza hesabu za biasharaAli Mwambola
Kuna wajasiriamali wengi ambao wamekuwa wanaanzisha biashara lakini hawana utaratibu wa kuweka hesabu za biashara zao.
Kutokuweka hesabu za biashara yako husababisha kutofahamu kama biashara yako inapata faida au hasara.
Kama huweki hesabu za biashara yako, huwezi kufahamu kama biashara yako inapanuka au inazorota. Vile vile huwezi kuelewa hali ya kifedha ya biashara yako
Usipoweka hesabu za biashara yako, unakuwa sawa na dereva unaye endesha gari wakati umefunika macho yako kwa kitambaa
Katika kazi yangu ya ushauri wa mambo ya biashara, nimekuwa nawauliza wajasiriamali kama biashara zao zinapata faida au hasara, wengi wao wamejibu kuwa hawafahamu
Majibu ya wajasiriamali ya kutotunza hesabu za biashara zao yamenisikitisha sana, hivyo nimefanya uamuzi wa kutunga hiki kitabu, kama mchango wangu wa kusaidia wajasiriamali watengeneze hesabu za biashara zao
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
Definition of Biopharmaceutics, Application of Biopharmaceutics, Definition of Absorption, Distribution, Metabolism, Excretion, Pharmacokinetics, pharmacodynamics, Bioavailability, Bio-equivalence, Plasma Concentration Vs Time Profile, Pharmacokinetics & pharmacodynamics parameters
Muhtasari wa kitabu cha jinsi ya kutunza hesabu za biasharaAli Mwambola
Kuna wajasiriamali wengi ambao wamekuwa wanaanzisha biashara lakini hawana utaratibu wa kuweka hesabu za biashara zao.
Kutokuweka hesabu za biashara yako husababisha kutofahamu kama biashara yako inapata faida au hasara.
Kama huweki hesabu za biashara yako, huwezi kufahamu kama biashara yako inapanuka au inazorota. Vile vile huwezi kuelewa hali ya kifedha ya biashara yako
Usipoweka hesabu za biashara yako, unakuwa sawa na dereva unaye endesha gari wakati umefunika macho yako kwa kitambaa
Katika kazi yangu ya ushauri wa mambo ya biashara, nimekuwa nawauliza wajasiriamali kama biashara zao zinapata faida au hasara, wengi wao wamejibu kuwa hawafahamu
Majibu ya wajasiriamali ya kutotunza hesabu za biashara zao yamenisikitisha sana, hivyo nimefanya uamuzi wa kutunga hiki kitabu, kama mchango wangu wa kusaidia wajasiriamali watengeneze hesabu za biashara zao
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
Patient medication adherence, Medication adherence, Causes of medication non-adherence, Problems linked with Medication Non-adherence, Factors affecting medication adherence, Patient related factors, Social and Economic factor, Disease related factor, Health care provider related factors, Therapy related factors, pharmacist role in the medication adherence, role of pharmacist in the medication adherence, monitoring of patient medication adherence, Direct method, Indirect method
hospital formulary is developed under the guidance of pharmacy and therapeutic commitee of the hospital.pharmacist working in a hospital should play an important role in the preparation of the hospital formulary
Introduction to clinical pharmacy, Concept and Objectives of clinical pharmacy, Function and responsibilities of clinical pharmacist, Clinical Pharmacy services.
COMMUNITY PHARMACY AND MANAGEMENT – CHAPTER -1................... (1).pptSumit Tiwari
A community pharmacy, often referred to as retail pharmacy or retail drug outlets, is places where medicines are stored and dispensed, supplied or sold
Patient medication adherence, Medication adherence, Causes of medication non-adherence, Problems linked with Medication Non-adherence, Factors affecting medication adherence, Patient related factors, Social and Economic factor, Disease related factor, Health care provider related factors, Therapy related factors, pharmacist role in the medication adherence, role of pharmacist in the medication adherence, monitoring of patient medication adherence, Direct method, Indirect method
hospital formulary is developed under the guidance of pharmacy and therapeutic commitee of the hospital.pharmacist working in a hospital should play an important role in the preparation of the hospital formulary
Introduction to clinical pharmacy, Concept and Objectives of clinical pharmacy, Function and responsibilities of clinical pharmacist, Clinical Pharmacy services.
COMMUNITY PHARMACY AND MANAGEMENT – CHAPTER -1................... (1).pptSumit Tiwari
A community pharmacy, often referred to as retail pharmacy or retail drug outlets, is places where medicines are stored and dispensed, supplied or sold
Med chem lecture on Anticholinergic drugs for B.Pharm level in Nepal
Content from Foye's Principle of medicinal chemistry, my own thoughts and some articles
Introduction
Have you ever thought about how does medicine move throughout your body? In this post, we will learn about the process of ADME in pharmacokinetics.
Suppose you have a headache and you take Disprin (Aspirin) tablet. But do you know how Dispirin knows where to go in your body or where the problem is?
Here, we will understand the entire journey of medicine in the human body. This post will be fascinating and informative for medical students, physicians, pharmacists, nurses, and general people.
So, keep reading to learn about ADME in pharmacokinetics –
What is meant by ADME in pharmacokinetics?
Pharmacokinetics is the branch of pharmacology (study of medicine) that deals with how drugs move through the body.
If we split the term pharmacokinetics. In Greek, “Pharmakon” means drug (or medicine), and “kinetics” implies movement.
In other words, pharmacokinetics is simply a movement of medicine in the body.
All medicines are indeed drugs, but not all drugs are medicines. So, medicine is considered a drug.
The pharmacokinetics would be basically an ADME study. The ADME in pharmacokinetics refers to absorption, distribution, metabolism, and excretion.
Every medicine must follow the ADME process (absorption, distribution, metabolism, and excretion). Here, ADME in pharmacokinetics -
A represents absorption – medicine gets into the bloodstream.
D represents distribution – medicine moves from the bloodstream to tissue (or site of action)
M represents metabolism – biotransformation of medicine (drug change from one form to another form)
E represents excretion – medicine eliminate from the body via urine/stool
What are the 4 steps of pharmacokinetics?
For a good pharmacokinetic profile, a medicine must complete 4 steps of pharmacokinetics in the human body, i.e., ADME.
Step 1 Absorption, Bioavailability & Prodrug
Step 2 Distribution
Step 3 Metabolism
Step 4 Excretion
- Routes of administration
- First pass metabolism, bioavailablilty, drug distribution,
- Drug interactions with proteins, Drug metabolism, elimination, Half-life
General pharmacology Diploma in pharmacy second year YogeshShelake
The General pharmacology ,Toxicology & Pharmacotherapeutics
To Undastanding the general pharmacology & Definitions of PHARMACODYNAMECIS ,PHARMACOKINITICS (Absorbation,Distribution,Metabolism,Excreation )Pharmacology ,Toxicology ,Pharmacotherapeutic ,
Advantages of Routs of Administration & Their Disadvantages
Factors affecting of absorpation ,excreation of drug,factor modifing deug action
This is the material for the 2nd week meeting on Food and Drugs Interaction for Nutrition students. This topic will cover the drug metabolism, looking at the pharmacokinetics and pharmacodynamics of drugs.
THIS VIDEO EXPLAINS ABOUT VITAMIN A IN EASY WAY
Important links- NOTES- https://mynursingstudents.blogspot.com/
youtube channel
https://www.youtube.com/c/MYSTUDENTSU...
CHANEL PLAYLIST-
ANATOMY AND PHYSIOLOGY-https://www.youtube.com/playlist?list...
COMMUNITY HEALTH NURSING- https://www.youtube.com/playlist?list...
CHILD HEALTH NURSING- https://www.youtube.com/playlist?list...
FIRST AID- https://www.youtube.com/playlist?list...
HCM- https://www.youtube.com/playlist?list...
FUNDAMENTALS OF NURSING- https://www.youtube.com/playlist?list...
COMMUNICABLE DISEASES- https://www.youtube.com/playlist?list...
ENVIRONMENTAL HEALTH- https://www.youtube.com/playlist?list...
MSN- https://www.youtube.com/playlist?list...
HINDI ONLY- https://www.youtube.com/playlist?list...
ENGLISH ONLY- https://www.youtube.com/playlist?list...
facebook profile- https://www.facebook.com/suresh.kr.lrhs/
FACEBOOK PAGE- https://www.facebook.com/My-Student-S...
facebook group NURSING NOTES- https://www.facebook.com/groups/24139...
FOR MAKING EASY NOTES YOU CAN ALSO VISIT MY BLOG –
BLOGGER- https://mynursingstudents.blogspot.com/
Instagram- https://www.instagram.com/mystudentsu...
Twitter- https://twitter.com/student_system?s=08
#VITAMIN_A,#FUNCTIONS,#SOURCE, #DEFICIENCY,#DISEASE,#NIGHTBLINDNESS#XEROPHTHALMIA,#BITOTSPOT,#CORNEALXEROSIS, #CONJUNCIVALXEROSIS, YELLOWFRUITS,#MYSTUDENTSUPPORTSYSTEM, #rashes,#nursingclasses, #communityhealthnursing,#ANM, #GNM, #BSCNURING,#NURSINGSTUDENTS, #WHO,#NURSINGINSTITUTION,#COLLEGEOFNURSING,#nursingofficer,#COMMUNITYHEALTHOFFICER
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.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
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!
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
for beginners, providing thorough training in areas such as SEO, digital communication marketing, and PPC training in Noida. After finishing the program, students receive the certifications recognised by top different universitie, setting a strong foundation for a successful career in digital marketing.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
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.
2. Core Areas of Pharmacy
1. Drug Design
Involves designing and synthesizing compounds to find a
specific chemical substances that will cure, manage or
prevent diseases: Cancer, AIDS, Ebola
2. Drug Formulation
Mix various chemical compounds with the drug to create
Tablet ,Suspension, Emulsion, Injection.
(These chemicals should not react with drug)
3. Drug Dispensing
Give the right drug to the right patient in right dose and
duration with sufficient counseling
(Biopharmaceutics has application on all three above)
4. Others (manufacturing,marketing and regulatory issues)
3. Drug?
• Drug is a specific organic compound which has
therapeutic effect (forget inorganic drugs like
MgOH from now on)
Metformin
Diabetis
Imatinib
Cancer
Lidocaine
Local Anesthetic
Paracetamol
Anti-inflamatory
Nelfinavir
AIDS
Omeprazole
Ulcer
4. Paracetamol
Anti-inflamatory
•How to consume?
•How much to consume?
•What happens if instead of 3 tablets, we take 6 or 9 tablets of
paracetamol on hopes of better or quicker recovery?
•How about we share a single tablet between two person?
•How much is too much or too less?
Understanding “Bio” in biophamaceutics
5. First of all….Pharmaceutics
• Pharmaceutics is science dealing with drug
formulation
• Drug formulation means process of mixing
drug with other chemicals to prepare a
physical form which facilitates convenient
dosing(intake) for patients
• That physical forms are Tablets, suspension,
emulsion, syrup or solutions. This is also called
oral dosing
7. Basic understanding of drug formulation
Formula of Paracetamol tablets
•Drug is never given in pure form but as an intended mixture with other chemicals to
help attain a physical form
•These other chemicals are called excipient
•Excipients don’t react with each other or with the drug
8. There are many choices for various excipient classes
from which many formulation of same drug in same
strength can be made
Excipient
Fillers/Diluent
(Allows making a
sizable tab if drug
content is very less)
Lactose,lactose anhydrous, lactose spray dried, directly
compressible starch,hydrolyzed starch, MCC, other cellulose
derivatives, dibasic calcium phosphate dihydrate, mannitol,
sorbitol, sucrose, calcium sulfate dehydrate, dextrose.
Binders
(allow drug power to
be compressed into a
solid tablet)
cellulose, methyl cellulose, polyvinyl pyrrolidine, PEG, gelatin,
PVP, HPMC, PEG, sucrose, starch
Disintegrating agent
(breaks hard solid tab
to free the power
drug from tablet)
starch derivatives, clay, cellulose, alginates, PVP, cross linked Na
CMCVeegum HV and Betonite PVP, CMC ,crospovidone, Sodium
bicarbonate
Lubricant Stearic acid, stearic acid salt, stearic acid derivatives, talc, PEG,
surfactants,waxes, Calcium stearate and magnesium stearate
poly ethylene glycol
Glidant talc, colloidal silicone dioxide, corn starch
9. First thing to do…..
• Understand that ALL drugs must be present in blood/plasma
to show effect (excluding topically (skin, eye, ear) applied
creams, gels etc)
• Depending on drug concentration in plasma either of three
results: no effect, therapeutic effect, side/toxic effect of drug
• This information is the first thing obtained during drug Human trials.
Thus we already know how much drug must be present in blood for
therapeutic effect to occur
• When we take a single dose, our interest is to provide just enough
drug to keep the drug conc within the therapeutic region
No effect Therapeutic effect Toxic effect
Effect of Increasing blood concentration on blood
10. Secondly, think about the time course of a drug
The drug conc in plasma varies continuously after we take a single dose
We cannot keep on maintaining drug conc in the therapeutic region by
only a single dose. Thus we need to give another dose
But what factors are making drug concentration to decrease and
How to know when to give another dose?????
11. • To make sense of above graph following
phenomenon have to be considered
– Absorption – drug enters blood circulation by
process of diffusion
– Metabolism – drug structure is enzymatically
altered
– Distribution – drug is distributed from blood to
fat, muscle, organs
– Elimination – Drug is thrown out from body
• Study of these 4 parameters is called
pharmacokinetics
12. Think about this!!!
• Now that we know what is the range of conc for a
drug to be in body, we could simply calculate the
amount of drug in a single dosage form
• Eg if paracetamol is to be maintainted at 50mg/Lt
plasma volume…considering an avg of 2.7 lt of
plasma in body, we could say that a single PCM
tablet needs to have 50X2.7= 135 mg
• However this type of assuption is wrong.
Determining amount of drug in a single dose is
not that simple because the body does not
behave like a vessel containing 2.7 lt of solvent.
• Body presents a dynamic environment to a drug
where the conc of drug is continuously changing
13. Understanding Absorption
Absorption occurs when drug dissolved in intestine diffuses through
the epithelium and into the capillaries (which is hepatic portal vein
which takes the drug to the liver)
(Notice the blood capillaries
into where drug diffuses)
14. Diffusion
• The spontaneous movement of solutes from high to low conc until
equilibrium is diffusion. It occurs in solution only.
• For purposes to study drug diffusion in body we consider diffusion
in the scenario where there are two compartments, left being
stomach and right being blood, and both being separated by the
lipophillic cell membrane epithelium
Let this compartment
represent drug dissolved
in stomach fluid
Let it represent
drug dissolved
in capillary
blood/plasma
Epithelium cell
membrane
15. Two opposing characteristic for good
absorption
• Diffusion through the epithelium requires crossing the
cell membrane of the epithelium which is lipophilic
barrier. This requires drug to have such structure
which gives it good lipophillicity.
• But since diffusion occurs only in solution, drug must
dissolve into the stomach fluid first. This requires drug
to have such structure which gives it good
hydrophillicity.
• (remember hydrophillicity and lipophillicity depend
are physiochemical properties that solely depend on
drug structure)
But drug is in form of a tablet. So how does a tablet dissolve?
16. Disintegrating agent!
• A tablet is a relatively hard substance. We
swallow it whole without chewing. That sounds
problematic (coz we always chew our food to
make digestion easy) but there are chemicals
added into the tablets called disintegrating agent
(in above Crosspovidone and Sod bicarbonate)
which swells up when in contact with water and
this causes tablet to break apart spontaneously.
• (Show tablet disintegration in a glass of water)
17. Show tablet disintregation in water
• Put various brands of 500mg paracetamol
tablets in water and observe that
– Tablet spontaneously breaks apart due to the
disintegrating agent soaks up water and expands,
thus causing tablet to break
– various brands disintegrate at different time and
to different degree
• This diff is due to diff in formulation which be
as we saw there are multiple choice for
particular excipients
18. Understanding Absorption is
important because….
• Many drugs have failed to be orally active
because they were too soluble and thus cant
permeate through the cell membrane
• Or they were too lipophillic and can’t dissolve in
stomach fluid (remember: diffusion requires drug
to dissolve in aqueous stomach fluid)
• Point is…..just cause we consume a drug doesn’t
mean there is guarantee of being absorbed
(however, for such problematic drugs,
formulation enhancement cab be done which we
will study later in course)
19. Metabolism
We saw that drug in a tablet
disintregates into smaller particles and
then dissolves to the extent depending on
its solubility which then diffusion through the epithelium into
the capillary. But it hasn’t quiet reached systemic circulation
• This capillary is names hepatic portal vein which goes to
the liver and then to the heart. As it flows through the liver
the drug are acted upon by special enzymes (other than
those involved in biological reactions) dedicated to
destroying endogenous substances.
• This is metabolism and it happens primarily in the liver
• The first time this happens is called 1st pass metabolism
and only applies to oral drugs
20. Metabolism of paracetamol
• Notice that paracetamol structure
changes- that is metabolism
• These metabolized products generally
lack any therapeutic use
• And are more water soluble for easy
removal by urine
Although it might seem that metabolism is a bad thing in that it destroys our drug,
We can overcome it by simply consuming more dose in compensation. Orally we can take
about 1gm dose. Any more compensation and the tablet would be too big to swallow
Also later on we will incredibly exploit this process in our favor in prodrugs
21. • Body responds to all endogenous substances, poison or
drugs, as if it were a threat and wants to detoxify them
and clear them out of body
• The enzymes alter the drug structure so that the
product is more water soluble.
• The increased water solubility is important since the
main path to clear the drug is through urine. Thus the
more soluble in urine, more quickly drug can be
cleared.
• Metabolism is another reason that any oral dose does
not fully reach the plasma as they get changed into a
diff compound along the way, even if absorption was
very good
• If liver get diseased causing reduced metabolism of
drugs then more drug are able to enter into the body.
This over exposure can cause toxic conc to build up!
22. Elimination
• Elimination can be seen as a two stage process
– 1st drug is metabolized by the liver into more water soluble form
– 2nd as blood flows through kidney, the now more water soluble form
is excreted (filtered) into the urine (an aqueous fluid)
• The more quickly elimination occurs, more quickly we need
another dose and vice versa
• Understand that without metabolism, excretion can difficult
cause drugs are mostly lipophilic
• So now we know that a drug action can’t be forever cause it
gets either destroyed by liver or excreted by kidney
• If kidney is damaged resulting in less filtration , than drug stays
in body for longer period of time!
• But what about giving drug to patients with both liver and
kidney damage?
23. Metabolism worked together with urinary excretion
Elimination also
occurs through bile
Oxidation and conjugation are two
types of metabolism that we will study later
Polar
Metabolite
go to urine
24. Distribution
Once drug passes through the liver it enter blood
circulation and can go everywhere the blood carries it
25. Distribution
Distribution takes place once drug has entered blood. As the pic
demonstrates of the given 10mg, only 1 mg is seen in the plasma. Thus
drug does not localized in the blood but can distribute itself out of
circulation into tissues, fat and even be bound to plasma protein.
Distribution is a problematic because, it lowers the conc of drug in
plasma and it is conc of drug and not the amount which determine
Once in blood , drug can go
to all places inside body
26. Long acting drug!!!
• An important concept is that distribution follows dynamic
equilibrium.
• Once distributed drug does not keep being trapped in fat,
tissues or plasma protein
• As the free drug in the plasma is metabolized and excreted,
the vacancy in plasma causes the distributed drug to again
come back to plasma
• In this way distributed drugs act like a reservoir which
sustains the conc in the plasma
• This can be exploited to make drugs with high distribution
so that they remain the body for a long period of time
compared to drugs that have low distribution (there is still
no way to avoid metabolism and excretion but this way
drug can act for a longer time period)
27. Conclusion
• We want drug to be within predefined conc range in blood
but we can’t simply treat body as a 5 lt vessel of blood.
• There are barriers for drug to maintain sufficient
concentration in plasma, in that they make sure that not all
the given dose can be reaches plasma (absorption) and
those that do reach plasma have difficult maintaining the
therapeutic concentration as drug is being structurally
altered (metabolism), diluted (distribution), kicked out
from the body (elimination)
• Thus we need to account for all these factors and decide
what should be the dose and frequency for every drug
cause these drugs have variable ADME
• This is the true essence of Biopharmaceutics
29. • Biopharmaceutics is defines as the study of
factors influencing the rate and amount of drug
that reaches the systemic circulation and the use
of this information to optimize the therapeutic
efficacy of drug products
• Biopharmaceutics concerns making such a
formulation of drug and defining its frequency of
dosing, by consideration of the ADME of a
drug,which ensures that the amount of drug in a
single dose (and repeated doses) achieves (and
then is maintained) in therapeutic drug conc in
plasma
30. • Pharmacokinetics is the study of time course of drug
ADME, and their relationship with it’s therapeutic, toxic
effects of drug
• Eg of Pharmacokinetic manipulation,
Distribution based -Vit k gelatin capsule is dosed at 60000
IU. Normal everyday dose is about 300-500IU. Thus 60 K IU
sounds to much (too much of anything is bad!!!) but won’t
be cause vit k being lipophillic gets stored in fat which is
released slowly in blood thus not only acting like a reservoir
of vit k but also ensuring small conc in blood. It means vit k
can be dosed once weekly but still body gets the needed
amount everyday
31. At last….
• A challenge in BioPham is to come up with a
method to predict time dependent changes in
drug conc
• They have been able to do that by building some
mathematical models (ie equation) that can
predict what would a drug conc be in any time in
body
(Don’t be afraid of the math portion. It’s the theory
that will be harder to comprehend. You probably
solved many tough problems based on equation of
motion; it is similar. There are some equation and u
just need to understand which one to use where)