The document discusses the mechanisms of drug absorption from the gastrointestinal tract. There are several mechanisms for drug absorption including passive diffusion, active transport, and paracellular transport. Passive diffusion is the most common mechanism and involves drugs crossing cell membranes down their concentration gradients without expending energy. Active transport mechanisms use energy to transport drugs against concentration gradients and include primary active transport using ATP and secondary active transport coupling to other ion gradients.

1. MECHANISMS OF
DRUG ABSORPTION
Presented By:
P. ALEKYA
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2.  INTRODUCTION
 DEFINITIONS
 MECHANISMS OF DRUG ABSORPTION
 CONCLUSION
 REFERENCE
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Drug treatment requires delivering a drug to its specific target site.
Typically, the drug is introduced into the body (the process
of administration), sometimes far from this target site.
The drug must move into the bloodstream (the process of absorption)
and be transported to the target sites where the drug is needed (the
process of distribution).
Some drugs are chemically altered (the process of metabolism) by the
body before they perform their action, others are metabolized
afterward, and still others are not metabolized at all.
The final step is the removal of the drug and its metabolites from the
body (the process of elimination).

4. ABSORPTION
The process of movement of unchanged drug from the site of
administration to systemic circulation.
There always exist a correlation between plasma concentration of a
drug & the therapeutic response & thus, absorption can also be
defined as the process of movement of unchanged drug from
the site of administration to the site of measurement i.e.,
Plasma.
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5. MECHANISM
OF DRUG
ABSORPTION
TRANSCELLULAR/
INTRA CELLULAR
TRANSPORT
PASSIVE
TRANSPORT
PROCESS
1. PASSIVE DIFFUSION.
2. PORE TRANSPORT.
3.ION-PAIR RANSPORT.
4.FACILIATED DIFFUSION
1.PRIMARY ACTIVE
TRANSPORT
2.SECONDARY ACTIVE
TRANSPORT
ACTIVE
TRANSPORT
PROCESS
PARACELLULAR/
INTER CELLULAR
TRANSPORT
PERMEATION THROUGH
TIGHT JUNCTIONS OF
EPITHELIAL
PERSORPTION
VESICULAR/
ENDOCYTOSIS
PINOCYTOSIS
PHAGOCYTOSIS
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6. It is defined as the passage of drug across the GI epithelium.
The three steps involve in the transcellular transport of drugs are:
a. Permeation of drugs across GI epithelium.
b. Movement of drugs across/through the cytosol.
c. Permeation of drugs through lateral or basolateral membrane.
1. PASSIVE TRANSPORT PROCESS
These transport process do not require energy.
A) PASSIVE DIFFISION:
It is also called as non-ionic diffusion.
Major process for absorption of more than 90% of drugs.
 Driving force – concentration or electrochemical gradient
 Difference in the drug concentration on either side of the membrane.
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Passive diffusion is best expressed by Fick’s first law of
diffusion which states that the drug molecule diffuse from a
region of higher concentration to lower concentration until
equilibrium is attained and rate of diffusion is directly
proportional to the concentration gradient across the membrane.

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9. Characteristics of Passive diffusion:
Energy independent.
Greater the area & lesser the thickness of the membrane, faster the
diffusion.
Concentration equal on both the sides of the membrane - Equilibrium is
attained.
Greater the partition coefficient of the drug faster the absorption.
But this is not the case……
The passively absorbed drug enters blood, rapidly swept away &
distributed into a larger volume of body fluids.
The concentration of drug at absorption site CGIT is maintained greater
than the concentration in the plasma. Such a condition is called as Sink
Condition for drug absorption.
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11. B) PORE TRANSPORT:
It is also called as Bulk Flow, Convective Transport or Filtration.
It is responsible for transport of molecules into the cell through the
protein channels present in the cell membrane.
Drug permeation through pore transport – renal excretion,
removal of drug from CSF & entry of drug into the liver.
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12. Characteristics Of Pore Transport:
The driving force – hydrostatic or osmotic pressure differences across
the membrane. Thus, bulk flow of water along with the small solid
molecules through aqueous channels. Water flux that promotes such a
transport is called as solvent drag.
The process is important in the absorption of low molecular weight
(<100D), low molecular size (smaller than the diameter of the pore) &
generally water soluble drugs through narrow, aqueous filled channels
or pores e.g. urea, water & sugars.
Chain like or linear compounds (upto 400D)- filtration.
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13. C) ION-PAIR TRANSPORT
Responsible for absorption of compounds which ionizes at all pH
values. e.g. quaternary ammonium, sulphonic acids.
Ionized moieties forms neutral complexes with endogenous ions
which have both the required lipophilicity & aqueous solubility for
passive diffusion.
E.g. Propranolol, a basic drug that forms an ion pair with oleic acid
& is absorbed by this mechanism.
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14. D) FACILITATED DIFFUSION:
 Facilitated diffusion is a form of carrier transport that does not require
the expenditure of cellular energy.
 Carriers are numerous in number & are found dissolved in cell
membrane
 The driving force is concentration gradient, particles move from a
region of high concentration to low concentration.
 The transport is aided by integral membrane proteins.
Facilitated diffusion mediates the absorption of some simple sugars,
steroids, amino acids and pyrimidines from the small intestine and their
subsequent transfer across cell membranes.
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16. B. ACTIVE TRANSPORT PROCESSES:
These transport processes require energy from ATP to move drug
molecules from extracellular to intracellular milieu.
a)PRIMARY ACTIVE TRANSPORT:
In this process, there is direct ATP requirement. Moreover, the
process transfers only one ion or molecule and in only one direction,
and hence called as uniporter .
e.g. Absorption of glucose.
Carrier proteins involved in primary active transport are of 2 types :
 Ion transporters.
 ABC transporters.
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17. Ion Transporter :
 Ion transporter are responsible for transporting ions in or out of cells.
A classic example of ATP driven ion pump is proton pump which is
implicated in acidification of intracellular compartments.
Two types of ion transporters:
 Organic anion transporter: e.g. Pravastatin.
Organic cation transporter : e.g. diphenhydramine.
ABC(ATP –Binding Cassette)transporter:
 ABC transporters are responsible for transporting small foreign
molecules especially out of cells i.e., exsorption which make them
clinically important.
 A classic example of ABC transporter is P- glycoprotein.
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18. b) SECONDARY ACTIVE TRANSPORT
In these processes, there is no direct requirement of ATP i.e. it takes advantage
of previously existing concentration gradient.
The energy required in transporting an ion aids transport of another ion or
molecule either in the same direction or in the opposite direction.
 symport(co-transport) : movement of molecules in the same direction.
Antiport(counter-transport): movement of molecules in the opposite
direction.
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Active transport is more important process than facilitated diffusion in the
absorption of nutrients and drugs.
 The drug is transported from region of lower to one of higher concentration
i.e., against the concentration gradient (in case of ions, against an
electrochemical gradient) or uphill transport.
 The process is faster than passive diffusion.
 Since the process is uphill, energy is required in the work done by the
carrier.

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It is defined as the transport of drugs through the junctions between the GI
epithelial cells.
These pathway is of minor importance in drug absorption.
The two paracellular transport mechanisms involved in drug absorption are :
A. Permeation through tight junctions of epithelial cells :
These process basically occurs through openings which are little bigger
than the aqueous pores .
e.g. Insulin and cardiac glycosides.
B. Persorption :
Permeation of drug through temporary openings formed by shedding of
two neighboring epithelial cells in to the lumen

22. It is a process in which involves engulfing extracellular materials within a
segment of cell membrane to form a vesicle .
Also termed as vesicular transport.
It occurs by 3 mechanisms:
Phagocytosis : (Cell eating)
Adsorptive uptake of solid particulates.
Pinocytosis : (Cell drinking)
Uptake of fluid solute. E.g. Sabine polio vaccine.
Transcytosis :
It is phenomenon in which endocytosis vesicle is transferred from
one extracellular compartment to another.
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IMPORTANT TRANSPORT FOR ABSORPTION

25. Oral route of drug administration is the most common for
systemically acting drugs and therefore, more emphasis will be
given to gastrointestinal(GI) absorption of drugs. Most of drugs are
absorbed passive diffusion mechanism having high lipophilicity
and the mol.wt in the range 100-400. some drugs , water-soluble
drugs of mol.wt less than 100 is absorbed by pore transport. Drugs
that ionize at all pH conditions absorbed after complexing with
oppositely charged ions that are absorbed through Ion- transport
mechanism. In carrier mediated transport structure specific drugs
with affinity for carriers transported from specific sites.
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26. 1. D.M.Brahmankar And S.B.jaiswal, Textbook of Biopharmaceutics and
Pharmacokinetics A treatise, Sixth edition, Vallabh Prakashan,
Pg.No.5-24.
2. C. V. S. Subrahmanyam, Textbook of Biopharmaceutics &
Pharmacokinetics, Second edition, Pg.No.80-149.
3. H.P.Rang And M.M.Dale Text book of Pharmacology, Sixth
Edition,Pg.No.98-102.
4. K.D.Tripathi, Textbook of pharmacology and pharmacotherapeutics,
Revised 21st edition,Pg.No:9-14.
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