for pharmacy

1. DRUG ABSORPTION FROM THE GIT
THUBOY
BPHARM (HONS), MPHIL
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2. OBJECTIVES
o Explain mechanisms by which drugs are
absorbed from the GIT
o Describe factors influencing drug absorption
from the GIT
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3. Introduction
o Absorption is the movement of a drug from its site of
administration into the central compartment.
o Diffusion of drugs through lipids usually determines their
rate of absorption
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4. METHODS BY WHICH DRUGS ARE ABSORBED FROM THE GIT
Depending on their chemical properties drugs may cross the membrane
from GIT by either of the following mechanisms.
1. Passive transfer
Simple diffusion
Filtration
2. Specialized Transport
Active transport
Facilitated diffusion
Pinocytosis
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5. PASSIVE TRANSFER
1. Simple Diffusion
o Simple diffusion means that a drug or substance is taken
across a membrane without the need for energy.
o Depends on the difference in concentration of the drug on
either side of the membrane, and the rate of diffusion is
directly proportional to the gradient.
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6. PASSIVE TRANSFER/SIMPLE DIFFUSION
o Both fat-soluble and water-soluble molecules of small size
may cross the membrane by simple diffusion, but lipid
soluble drugs diffuse most rapidly.
o It is not saturable.
o Does not show structural specificity
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7. PASSIVE TRANSFER
2. Filtration
o This occurs when a porous membrane exists which
allows the flow of substances of a certain size only,
with the larger size being blocked.
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8. Specialized Transport
1. Active transport
o Refers to a situation when the drug is moved against a
concentration gradient by the use of energy and is
driven by the hydrolysis of ATP.
o Limited to drugs structurally similar to endogenous
substances.
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9. Specialized transport
2. Facilitated diffusion
o A unique form of transport in which the drug reversibly attaches to a
special “carrier” which facilitates diffusion across the membrane, and
then releases the drug.
o The drug is not chemically altered and carrier freed to carry further
drug transfer. Availability of carriers limit the process
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10. Specialized transport/facilitated diffusion
o The membrane transports only substrates with a specific
molecular configuration.
o This process does not require energy.
o It can only work in the presence of an appropriate
concentration gradient.
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11. Specialized transport/facilitated diffusion
Carrier mediated transport is also important in:
◦ The blood brain barrier
◦ The renal tubule
◦ The biliary tract
◦ The placenta
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12. Specialized transport
3. Pinocytosis
o Describes the ability of cells to surround and engulf small
droplets.
o This process is important in the uptake of large molecules e. g
protein drugs.
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13. Factors influencing absorption
1. Physiological Factors
1.1 pH
Most drugs are organic acids or bases, and at physiological pH of body
fluids ( 7.35-7.45), drug molecules exist as a mixture of the non-ionised or
and the ionized form.
The degree of ionisation depends on the pKa of the drug and the
surrounding pH.
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14. Physiological Factors influencing absorption
o Absorption of unionized molecules is favored because they
are far more lipid soluble than those that are ionized.
o Ionized drugs are more water soluble and less lipid soluble.
o Cell membranes are more permeable to the non-ionized
form than to the ionized form of the drug.
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15. Physiological Factors influencing absorption
• Acids are most highly ionized at a high pH (i.e. in an alkaline
environment). Bases are most highly ionised in an acidic environment
(low pH).
• For a weak acid, the more acidic the environment, the less ionized
the drug, and the more easily it crosses lipid membranes. If you take
this acid, at pKa it is 50% ionised, if you add 2 pH points to this (more
alkaline), it becomes 90% ionised, if you reduce the pH (more acidic)
by two units, it becomes 10% ionised. Weak bases have the opposite
effect.
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16. Physiological Factors influencing absorption
1.2 Blood flow to site of absorption
o Blood flow in the intestine is higher than in the stomach, so
generally there is more drug absorption in the intestine than
stomach.
o Blood flow affects rate of clearance of drug from site of absorption.
o Some drugs are absorbed in the stomach and others in the intestine.
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17. Physiological Factors influencing absorption
1.3. Total surface area available for absorption
o Intestine has larger surface area than the stomach, 1000x
more than stomach. Because intestine surface is rich in
microvilli.
o Therefore drug absorption across the intestine is more
efficient.
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18. Physiological Factors influencing absorption
1.4 Contact time at site of absorption surface
o If drug moves through GIT very quickly, as in severe diarrhea
it is not well absorbed.
o Conversely anything that delays movement of drug from
stomach to intestine (gastric emptying) delays absorption.
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19. Physiological Factors influencing absorption
1.5 Stomach contents
Presence of food :
◦ Slows gastric emptying and
◦ Also dilutes drug concentration, thus delays drug absorption.
◦ Formation of complexes with drugs hence hampering their
absorption e g calcium and milk.
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20. Physiological Factors influencing absorption
1.6 Disease status
Diseases which affect the morphology and physiology of
the GIT can affect the rate of drug absorption, e g Crohn’s
disease.
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21. Factors influencing absorption
2. Physico-chemical factors
2.1 Molecular weight of drug
o Drugs with large molecular weight are not usually absorbed
intact except in minute quantities.
o They may be broken down by enzymatic action e. g proteins
to amino acids, before absorption.
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22. Physico-chemical Factors influencing absorption
2.2 Chemical stability
o Unstable drugs are inactivated in the GIT e. g benzylpenicillin
is unstable in acid medium and therefore absorption is poor
because inactivacted by acid in the stomach.
o In contrast phenoxymethylpenicillin is more stable and well
absorbed.
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23. Physico-chemical Factors influencing absorption
2.3 Lipid solubility
Cell membranes are lipid by nature, the degree and rate of
penetration of the drug through them is dependent to a
large extent on the lipid solubility of the drug.
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24. Physico-chemical Factors influencing absorption
2.4 Degree of ionization
• Most drugs are either weak acids or weak bases
• At any time some of the drug is ionised and some is non-
ionised.
• The rate and degree of absorption will depend on the
proportion of the two forms.
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25. Physico-chemical Factors influencing absorption
2.5. Pharmaceutical formulation
o Formulation of a drug can influence the amount and rate of
absorption.
o Solutions are better absorbed than tablets and suspensions.
o Particle size of powder, additives etc used in a tablet affects its
disintegration and dissolution rate and hence absorption.
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26. Physico-chemical Factors influencing absorption
Small particle size are absorbed faster than large
size due to better wetting and therefore
dissolution.
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27. Textbooks
o Basic and Clinical pharmacology 10th Edition, B. G.
Katzung
o Intergrated Pharmacology 3rd Edition, Page et al
o Rang and Dale’s Pharmacology 8th edition
o Medical pharmacology and therapeutics 4th Edition, D.
G. Waller
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