MECHANISM OF DRUG ABSORPTION

1. ROHIT MISHRA
M.PHARM
PHARMACEUTICS
GLA

2. The process of movement of
unchanged drug from the siteof
administration to systemic
circulation.
What is Drug Absorption

3. MECHANISMS OF
DRUG ABSORPTION

4. I. PassiveDiffusion
 Diffusion
 Movement fromhigh
low concentration
• Major process for absorption
of more than 90% of drugs
• Non ionic diffusion
• Driving force – concentration
or electrochemical gradient
• Difference in the drug
concentration on either side
of the membrane
• Drug movement is a result of
kinetic energy of molecules

6. Mathematically(Fick’s First law of
diffusion)
.................I
dQ/dt = rate of drug diffusion (amount/time)
D = diffusion coefficient of the drug
A= surface area of the absorbing membrane for drug diffusion
Km/w = partition coefficient of drug between the lipoidal membrane &
the aqueous GI fluids
(CGIT – C) = difference in the concentration of drug in the GI fluids &
the plasma (Concentration Gradient)
h = thickness of the membrane

7. Characteristics of Passive diffusion:
Energy independent
Greater the area & lesser the thickness of the membrane, faster
the diffusion
The process rapid over for short distances
Concentration equal on both the sides of the membrane -
Equilibrium is attained
Greater the PC of the drug faster the absorption

8. ii. PoreTransport
• It is also called as convective transport, bulk flow or filtration.
• Mechanism – through the protein channel present in the cell
membrane.
• Drug permeation through pore transport – renal excretion, removal
of drug from CSF & entry of drug into the liver

9. 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

10. iii. Ion-PairTransport
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

11. Carrier MediatedTransport
• Involves a carrier
which reversibly
binds to the solute
molecules and forms a
solute-carrier
complex.
• This molecule
transverse across the
membrane to the other
side and dissociates,
yielding the solute
molecule.
• The carrier then
returns to the original
site to accept a new
molecule.
• There are two type of
carrier mediated
transport system
1) Facilitated
diffusion
2) Active transport

12. FacilitatedDiffusion
• 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 conc to low
conc.

13. Contd…
• 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.

14. ActiveTransport
• Requires energy, which is
provided by hydrolysis of
ATP for transportation.
• More commonly,
metabolic energy is
provided by the active
transport of Na+, or is
dependent on the
electrochemical gradient
produced by the sodium
pump, Na+/K+ ATPase
(secondary active
transport).

15. This transport requires energy in the form of ATP

16. Primary ActiveTransport
• Direct ATPrequirement
• The process transfers only one ion or molecule & only in
one direction. Hence, called as UNIPORT
• E.g. absorption of glucose
• ABC (ATP binding Cassette) transporters

17. Secondary ActiveTransport
• No direct requirement ofATP
• The energy required in transporting an ion aids transport of
another ion or molecule (co-transport or coupled transport)
either in the same direction or opposite direction.
• 2 types:
• Symport (co-transport)
• Antiport (counter transport)

18. symportantiport
ATP ATP
Antiport and Symport

19. Endocytosis
• It is a process in which
cell absorbs molecules
by engulfing them.
• Also termed as
vesicular transport.
• It occurs by 3
mechanisms:
Phagocytosis
Pinocytosis
Transcytosis

20. Phagocytosis

21. Pinocytosis
• It is a form of endocytosis in
which small particles are
brought to the cell, forming an
invagination.
• These small particles are
suspended in small vesicles.
• It requires energy in the form
ofATP.
• It works as phagocytosis, the
only difference being, it is non
specific in the substances it
transports.
• This process is important in
the absorption of oil soluble
vitamins & in the uptake of
nutrients

22. References
D.M Brahmankar and Sunil B. Jaiswal, Biopharmaceutics and
Pharmacokinetics: A Treatise 2009 second edition Published by
M.K Jain for Vallabh Prakashan New Delhi Page number 1-23