PHARMACOKINETICS:

I.ABSORPTION

This is not a LECTUREthis is

a discussion sadly not live !!!
PHARMACOKINETICS
Objective
is not to bombard
information but to develop
concepts. Dr.B.M.PUROHIT
Professor (Pharmacology)
So.. GetAssistant
ready
to
chat
!!
P.D.U.MEDICAL COLLEGE,
Rajkot (GUJARAT). 360001
purohitbhargav@rediffmail.com

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 This topic is universally accepted as

BORING !!
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MOVEMENT

WHATS NEW ABOUT IT ?? ..NOTHING !!

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boring !!!
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ABSORPTION
First step.

CROSS
BIOLOGICAL MEMBRANES

For that drug has to

at

numerous sites.
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Absorption

Excretion

Unwanted site of
action
Free bound

FREE DRUG
Protein
METABOLIT
bound
ES
CENTRAL COMPARTMENT
Biotransformation

Site of action
Free bound

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TISSUE RESERVOIR
Free bound

 Puzzled ?
Need a revision ??
Remember .go slow and as
you read, go on remembering it
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Absorption

Excretion

Unwanted site of
action
Free bound

FREE DRUG
Protein
METABOLIT
bound
ES
CENTRAL COMPARTMENT
Biotransformation

Site of action
Free bound

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TISSUE RESERVOIR
Free bound

SUMMARY OF DIAGRAM
So after absorption.
A part may get excreted unchanged.
A part may be metabolized and than excreted.
excreted
A part will reversibly bind with the site of
action.
action
A part will reversibly go to tissue reservoirs.
reservoirs
A part will reversibly go to unwanted site of
action.
A part will reversibly bind with plasma
proteins.
proteins
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All this things happen after ABSORPTION

Million dollar question..

How EXTERNALLY administered drug

CROSSES BIOLOGICAL
MEMBRANES ? ( THEIR MOLECULAR MECHANISMS).

Now imagine a molecule trying to cross a

biological membrane.
membrane

So a molecule and a membrane are fighting with

each other !!!!
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Dont
requir
e
energ
y

Requi
re
energ
y

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SUMMARY
Drug crosses membrane by diffusion
and membrane transporters..
Diffusion can be lipid or aquous
Membrane transporters can be
facilitated or activated.

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PHYSICAL PROPERTIES

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DOSAGE FORMS

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Better
paramet
er

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 Lets revise drug related factors

Physical properties
Physical state
Lipid or water solubility

Dosage forms
Particle size
Disintegration and dissolution rate
Formulation
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IONIZATION

TAKE HOME MESSAGE ..

UNIONIZED FORM IS BETTER

ABSORBED..store it youre
your hard disk !!!!!
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pH

Although acidic drug are better

absorbed from stomach , a large
portion of it gets absorbed through
the intestine because of greater
surface area it provides.

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GI transit time

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PRESENCE OF FOOD

To be
taken
after
meals

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To be
taken
before
meals

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ENTEROHEPATIC
CIRCULATION
Increases the bioavailability.
Morphine

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Area of the absorbing

surface and local circulation

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FIRST PASS METABOLISM

Metabolism between site of absorption
to that of systemic circulation.
Decreases the bioavailability of drugs.
It takes place in
Gut wall
Liver
Skin
Lung
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PRESENCE OF OTHER
AGENTS
IRON ABSORPTION

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FAT SOLUBLE VITAMINES ABSORPTION

REDUCED IN THE PRESENCE OF LIQUID
PARAFFIN

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DISEASE CONDITIONS

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 Which are drug releated factors affecting drug

absorption ?
Physical properties
Dosage forms.
Which patient related factors
Ionization
pH
GI transit time
Presence of food
Enterohepatic circulation
Area of absorbing surface
First pass metabolism
Presence of other agents.
Diseased conditions

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SO ABSORPTION PART
IS OVER

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BIOAVAILABILITY
percent of administered drug reaching systemic
circulation following nonvascular administration.
E.g. if 500 mg drug is given and 50 mg reaches
systemic circulation bioavailability is 10%.
It is important in .
Drug with low safety margin.(
margin e.g. digoxin)
Drug where specific plasma levels are
necessary.
necessary (oral hypoglycemic, oral
anticoagulants, oral antiepileptics)
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concentration

Minimum toxic
concentration

Minimum effective
concentration

Time

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AUC after oral dose

Bioavailability(%) =

100

AUC after IV dose

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 IV administration Bioavailability
will be 100 %.
Oral administration BA
decreases because of..
Incomplete absorption
First pass metabolism.

SC or IM administration
Incomplete BA after injection
occurs because of local binding of
drug.
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All
processe
s of!! GO ON
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PK !!! !!!

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For every two market formulations of the same active drug,

bioavailability will be DEFINITELY DIFFERENT.

This difference may not be CLINICALY SIGNIFICANT.

SIGNIFICANT

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So AS FAR AS
POSSIBLE AVOID
CHANGING
BRANDS in
SUCH CASES.

Drugs like
anticoagulan
ts,
antiepileptics
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NOW ITS TIME TO REVISE

What is bioavailability ?
When this parameter becomes
significant ?
What is difference between BA of IV,
oral, SC or IM route?
What is chemical equivalent ?
What is biological equivalent ?
Which factors affect bioavailability ?
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MEMBRANE TRANSPORT
Bilayer of phospholipid and
cholesterol.
Polar groups on surfaces
Non polar groups in matrix.
Extrinsic and intrinsic protein are
adsorbed on lipid bilayer.
Proteins freely float through the
membrane.
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FILTRATION
Through pores.
Generally pores are small except
capillaries.
MW<100 can pass through it.
Capillaries have large pores, except
BBB.

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DIFFUSION
Higher
conc.

M
E
M
B
R
A
N
E

Lower
conc.

DIFFUSION
Lipid soluble

Water
insoluble
FILTRATION

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AQUEOUS DIFFUSION

LIPID DIFFUSION

Most biological
membranes are water
permeable.
In gut, cells are joined
tight epithelial
junction, water passes
through the cells.
Water carries water
soluble substances of
LMW.
Urea, alcohol

Hydrophobic lipid
substances are
dissolved in this
manner.
O2,CO2,N2, unionized
substances.

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 Passive diffusion occurs through..

through
Concentration gradient
Lipid solubility.

Lipid solubility ~ ionization

Ionized water soluble not
absorbed.
Unionized lipid soluble better
absorbed.
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