Outline the drug absorption

process
 What is drug absorption?
 Absorption is the process by which a drug passes
from its site of administration into the circulation
(bloodstream).

 The blood receives a drug from the site of

administration and carries it to all the organs,
including those on which the drug acts

 The speed, ease and degree of absorption are

related to the route of administration.
Absorption process depend on-
 Routes of Administration
 Barriers to Diffusion
 Factors that affect Drug
Absorption
a. Factors related to drugs
b. Factors related to patient
 Affect of pH on drug absorption.
Routes of Administration
 Oral
Advantage: Convenient Efficient Absorption (huge
surface area)
Disadvantage: Drug degradation, Requires lipid
permeation, Gastric irritation. First pass effect
 Inhalation
Advantage: Large surface area ,Access nasal or lungs ,
Rapid delivery to blood
Disadvantage: Requires special properties (vaporized,
atomized)
Nasal proteases , Irritation
Route of Drug administration
 Intravenous
Advantage: Direct, Rapid ,Programmable
Disadvantage: Hazardous, Requires professional
 Intramuscular
Advantage: Rapid for aqueous ,Slow depot for oil
Disadvantage: Pain, inflammation at delivery site
 Subcutaneous injection
Advantage: Rapid, no gastric irritation, bypass first pass
effect
Disadvantage: water soluble and irritating drug can’t use
 sublingual
Advantage: Rapid , Self administered, No first pass effect
Disadvantage: Small doses, unpleasant taste, Drug must be
lipid soluble and potent
 Rectal:
Advantage: Suitable in extreme ages, avoid gastric irritation
Disadvantage: patients don’t like this route, irritate in rectal mucosa
 Transdermal
Advantage: Prolonged Release
Disadvantage: Lipid permeation, Initial time lag, Dermal
enzymes
 Others: Intrarteria, Intrathecal, Intraperitoneal
 Barriers to Diffusion
Depending on the chemical properties drugs may be absorbed from
GI tract by passive diffusion, active transport, pinocytosis process.
Passive diffusion:
 It is the commonest and important process
 Require no energy
 Depends on-

i. Conc. Gradient
ii. Lipid /water partition co-efficient
iii. Molecular wt & size of drugs
iv. pKa of the drug and pH of the local fluid
Example- Aspirin, barbiturates, Morphine
Drug Absorption by passive
diffusion
Active transport
 Occurs against concentration gradient.
 Requires carrier & energy
 Occurs in case of drug resembling natural substrate
 Specific & relatively unstable
 Depends on lipid/ water partition co- efficient
 The carrier system may be saturated at high concentration
 The process is competitive ( i.e. drugs with same structure may
compete for the same career
Example: Amioacids, Nucleic acid & Iron
Endocytosis:
Transport process of
large molecule

Requires energy,
calcium, contractile
elements of cell

Independent of lipid/
water partition co-efficient.

Example: Sucrose, Insulin

Active Transport Diffusion
 Factors that affect Drug
Absorption

 Factors related to drugs

a. Molecular wt: Drug absorption is
inversely proportional to m. w. Low
molecular wt drug can easily pass through
small pores.
b. Molecular size: Drug absorption is
inversely proportional to molecular size,
smaller the size of drug the more will be
absorption.
c. Lipid/water partition Co-efficient:
Increase lipid solubility  Increase absorption
Increase duration of action
Increase water solubility Decrease absorption
Decrease bio-availability
d. Ionization constant (Pka):
Increase ionization More water solubility
Decrease absorption
Decrease ionization Less water solubility
Increase absorption.
e. Formulation: Different rate of absorption for different
formulation
f. Disintegration time: Increase disintegration time
Decrease absorption
g. Dissolution: Increase dissolution Increase absorption
 Factors that related to patient:

a. pH of the gut:
In acidic Ph, acidic drugs  Less ionized
 Increase absorption.
In alkaline ph, basic drugs Less ionized
 Increase absorption
b. Time of administration: Increase the rate of
gastric emptying Increase absorption. Empty
stomach increase absorption of antibiotic
increase bio-availability. Full stomach Increase
absorption of iron increase bio-availability
c. Bowel transit time: Increase intestinal motility
Decrease absorption

d. Mucosal surface area: Increase surface area

Increase absorption.
e. Gastrointestinal disease:
Crohn’s disease, Coeliae disease Increase
absorption
Gut oedema with CCF Decrease absorption
f. Presence of food flow: Food interfere with
absorption of water soluble drugs, again high
lipid soluble drugs are better absorbed in
presence of food.
g. Regional blood flow: Increase blood flow
Increase absorption.
h. Inactivation: Inactivation of drug by gut
enzyme Decrease absorption.
i. Drug interactions: When two or
more drugs are administrated
simultaneously one drug will affect the
absorption of other. Tetracycline+
Antacid Decrease the absorption of
tetracycline.
j. Area of absorption surface:
Increase surface Increase
absorption increase bio- availability.
 Affect of pH on drug absorption.
• The relationship of pKa and the ratio of acid- base
concentrations to pH is expressed by the Henderson -
Hasselbalch equation

• This equation is useful in determining how much drug will

be found on either side of a membrane that separates
two compartments that differ in pH.
 Affect of pH on drug absorption.
Drug is weak acid
AH A-+H+
 Acidic environment : protonated, un-ionized, lipid-
soluble.
 Basic environment : un-protonated, ionized, water
soluble
Drug is weak base
BH+ B+H+
 Acidic environment : protonated, ionized, water
soluble.
 Basic environment : un-protonated, un-ionized, lipid-
soluble.