Gastrointestinal absorption of drugs

and its biological considerations

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Gastrointestinal absorption of
drugs
 Gastro intestinal barrier( lipoidal sieve) that separates
lumen of the stomach and intestine is a semi permeable
membrane, permitting the rapid and limited passage of
some compounds.

Gastro intestinal absorption is more for some nutrients

glucose, amino acids, fatty acids &vitamins etc.

lipid molecules and some hydrophilic molecules are

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readily absorbed from git in passive manner where as large
Mechanism of gastro intestinal absorption

Passive diffusion

Carrier mediated absorption

 Active
 Facilitated
Endocytosis

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Passive Diffusion :
Membrane transport of drug and other chemicals directly
through the lipid or aqueous channel is called passive
diffusion
It follows FICKS FIRST LAW of diffusion.
It states drug molecule diffuses from a region of higher
conc. to the lower conc. until equilibrium is attained.
dc/dt = k(C1-C2).
dc/dt : rate of diffusion
C1C2 = drug concentrations on each side of the
membrane. 4
Pore transport and ion pair
transport:
It is also called as convective transport, bulk flow or
filtration. the process is important in the absorption
of low molecular weight(less than100),low molecular
size(smaller than diameter of the pore).for eg-
urea,water,and sugars.
Ion-pair transport-that explains the absorption of
drugs like quaternary ammonium compounds and
sulphonic acids, which ionize under all PH conditions,
is ion –pair transport.

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Carrier Mediated Transport :
The compound involved is called CARRIER.
The carrier binds non covalently or reversibly with solute
molecule to be transported.
It is specialized transport mechanism with out which
many essential water soluble nutrients like mono
-saccharides will be poorly absorbed.
The carrier solute molecule complex travel across the
membrane to other side where it dissociates and
discharges the solute molecule and travels back.
It follows mixed order kinetics.
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Facilitated diffusion:

This carrier mediated transport system that

operates down the concentration gradient (down
hill transport).
It is faster than passive diffusion.
Driving force is conc. gradient.
Ex: vitamins.

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Active Absorption:
 It requires energy in the form of A.T.P.
Takes place in the intestine
This is a UP HILL TRANSPORT.
Ex: Na,Ca,Fe, glucose, galactose, AA, Bile salts.
Rate of absorption = VmaxC/Km+C.
C=solute conc. at the absorption site.
Vmax and Km are const.
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Endocytosis:
It is a minor transport mechanism which involves
engulfing extracellular materials within a segment of
cell membrane to form a saccule or a vesicle.
This phenomenon is responsible for the cellular
uptake of macromolecular nutrients like fats and
starch, oil soluble vitamins & water soluble vitamins.
It include two type of processes:

Phagocytosis(cell eating): absorptive uptake of solid

particulates.
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BIOLOGICAL FACTORS :

Age
Gastro intestinal physiology.
Gastro intestinal blood flow.
Gastro intestinal PH.
Gastric emptying.
Effect of food on drug absorption.
Disease states 10
AGE :
In infants, the PH gastric is high and intestinal
surface and blood flow to the GIT is low resulting in
altered absorption pattern in comparison to adults.
In elderly person,causes of impaired drug absorption
include altered gastric empting, decreased intestinal
surface area and GI blood flow, higher incidents of
achlorhydria and bacterial overgrowth in small
intestine.

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Gastro Intestinal Physiology :
STOMACH :

It is a pouch like structure
lined by smooth epithelial
membrane.

Absorption of weekly acidic
drugs or un ionized drugs
and week basic drugs takes
place.

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Small intestine :
generally carrier mediated
Click to edit Master
transport is seen in most
text styles
drugs.
Second level
 Third level
Proximal part-absorption
 Fourth level
of dietary constituents
 Fifth level includes mono saccharides,
vitamins, minerals etc.
Ileum-Vit B12, bile salts.

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 Micro villi :

The effective surface area
Click to edit Master text can be made 10 times larger
styles to that of stomach because
Second level of the presence of micro
 Third level villi.
 Fourth level 
These are finger like
 Fifth level
projections arising from and
forming folds in intestinal
mucosa.

ESA was decreasing from
proximal part to distill part
of small intestine. 14
Large intestine : 
ESA was less.
Click to edit Master text 
It is not an effective site
styles 
In complete absorption was
Second level
occurred when large
 Third level
amount of drug reaches
 Fourth level colon
 Fifth level

Its an area of absorption of
escaped drug

It was recommended for
certain drugs whose
metabolism occurred by
intestinal bacteria for bio
activation.
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BLOOD FLOW :
It plays a major role in absorption by
continuously maintaing the concentration
gradient across the epithelial membrane.
Absorption of polar molecules doesn’t
depends on the blood flow.
 Rate of drug absorption is un effected by
mesenteric blood flow.
Absorption of lipid soluble molecules highly
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depends on the blood flow.
Gastro intestinal PH :
PH varies according to the site.
Many drugs are week organic acids or bases so PH
is the imp factor.
Gastric fluid retards week basic drugs.
and promotes weekly acidic drugs.
Gastric secretions having PH less than 1.
It varies because of diet and dilution.
ex: penicillin-------------carindacillin
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erythromycin--------erythromycinesfolate
Gastric emptying :
The passage of food from the stomach to the
small intestine is called gastric emptying.
This process increases the bioavailability of the
drug because mostly the absorption occurs in
small intestine.
Slow gastric emptying can delay the onset of
effect of the drug Ex: Analgesics & sedatives

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FACTORS EFFECTING GASTRIC EMPTYING :

Volume of meal.
Drugs
Posture
Composition of meal.
Physical state.
Temperature.
PH.
Disease state. 19
Effect of food on drug absorption :

Food stimulate hepatic blood flow, which

have implication for the bioavailability of
the drug.
Food tends to decrease the rate of gastric
emptying which effects drugs like
penicillin
Forms poorly soluble and un absorbable
complexes. 20
Disease states :
There are three classes of disease state

1. Gastrointestinal diseases –It influence drug

absorption pattern, namely:
Altered GI motility:

Gastrointestinal diseases and infections

Gastrointestinal surgery

2. Cardiovascular diseases
3.Hepatic diseases 21
Presystemic Metabolism:

The loss of drug through biotransformation by such

eliminating organs during its passage to systemic
circulation is called as first pass or
presystemic metabolism.
The 3 primary system which affect presystemic
metabolism of a drug are :
 Luminal enzymes : the metabolism by these enzymes
are categorized into two-
Digestive enzymes, and Bacterial enzymes.
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
Mal absorption :
It is a disorder with impaired absorption of fat,
protein, carbohydrate, vitamin, minerals& water.
Drugs which induce mal absorption:

N Neomycin.eomycin.

Phenytoin.

Amino salicylate

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These drugs mainly damages the gastro intestinal
Mal absorption
Click to edit Master text
styles
Second level
 Third level
 Fourth level
 Fifth level

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References:
 Biopharmaceutics and pharmacokinetics by madan
published by Jaypee publication 1st edition page 62-
67.
 Essentials of Biopharmaceutics and pharmacokinetics
by Ashutosh kar,published by Elsevier health sciences
2010 page no-642-657.
 Biopharmaceutics and pharmacokinetics by
D.M.Brahmankar and Sunil B.Jaiswal ,vallabh
Prakashan ,second edition ,page no-65-78.
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Thank you

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