DRUG ABSORPTION

- An irreversible process which transfers a drug from its site of administration to the systemic
circulation.

1. Affects the solubility of the drug and the rate and extent of absorption of the drug.
2. The design affects absorption

The release and liberation of a drug is dependent on its (physicochemical factors) solubility,
environment in the human body at the site of administration and pharmaco-technical factors.
Adsorption – If drugs are administered through the skin.

Penetration – the drug reaches the deeper layer of the skin but does not reach the blood capillaries.

Permeation – the drug is already inside/already reaches the general circulation.

Absorption – absorption only occurs only if the drug permeates through the capillary walls and
enters the blood stream.
Only physiologic will be discussed

Intravascular – the drug is placed directly into the

blood stream.

Extravascular – the drug undergoes an absorption

process before it reaches the systemic circulation.

- Has two types

Extravascular parenteral route

- Intramuscular and sub-cutaneous

Extravascular non-parenteral route

- Oral, rectal, vaginal, and topical.

IV is available in the blood stream at its maximum concentration (advantage) but once it causes
toxicity then it’s hard to reverse. (disadvantage)
Orally administered doses must release its contents in the GI before becoming available for
absorption but toxicity is easier to reverse compared to IV. Oral drugs take a long time to have an
effect in the body.

this is
found in
the book.

The most
common

intravascular route of administration – IV

The most popular and common extravascular route of administration – oral

The most popular extravascular parenteral route – intramuscular

 Orally administered drugs are
potentially absorbed in the buccal
activity and gastrointestinal tract.
Absorption of drugs from the
gastrointestinal tract can occur in
the stomach, small intestine, large
intestine, and the rectum but
among all these sites, the small
intestine is a common area for drug
absorption for orally administered drugs since the small intestine has a greater surface area.

The small intestine also has good blood flow.

The factors that may affect absorption at the site of absorption:

- Drug instability in the GI tract (first-pass effect) which is high hepatic clearance
- pH
- degradation of the drug by the digestive enzymes

Buccal cavity and rectum administered drug bypasses initial biotransformation which is first pass
effect.

The limiting factor is the cell membrane

(major structure of cells surrounding the
entire cell and acting as a boundary between
cells).

The permeability of the membrane can affect

the absorption of the drug.

there is tension between oil and water meaning

they wont be mixed. Surface tension may affect the
absorption of the drug.

Electric molecules with a charge that is different

with the charge of the membrane will result to a
repulsive action that affects drug absorption.

Surfactants can increase the permeation or the

movement of drugs through the cell membrane.
 1. passive diffusion
2. Active transport
3. Facilitated transport
4. Convective transport
5. Ion pair transport
6. Vesicular transport

Passive diffusion – it is through a semi-

permeable membrane.

- No external energy is expended.

- Most common transport mechanism.
- Follows a fixed law of diffusion

free – must not be protein bound.

increase surface area will also increase drug absorption… is only true for oral drugs.

Thickness of the membrane is constant but their permeability in the different locations will affect the
rate of diffusion.

The higher the diffusion coefficient, absorption is increased thus improved systemic bioavailability in
the systemic circulation.

Against concentration gradient – it needs energy

become saturated – when the carrier is hurot

1. Much greater than concentration of a drug at the site of absorption

B vtamines, cardiac glycosides, strong organic acids, strong organic bases are drugs that are
transported via active transport (watch)
 1.5mcg of B12 are absorbed by the
facilitated transport system.

4. also known as pore transport

because it transports drug
molecules through the pores of
biological membranes.

Example of Facilitated Transport

- absorption of vitamin B12. (B12 will form a complex with intrinsic factor that is produced in the
stomach wall and then it will be transversed in the membrane.

Facilitated transport plays a minor role in the drug absorption.

In convective transport, the drugs dissolve in the aqueous medium of the pores at the site of
absorption and it moves along the solvent through the aqueous pore.

The movement of the drug with solvent through the pores is termed as shifting of the solvent.

The aqueous pores in the biological membrane has a diameter in the range of 7 to 10 arm strong.
Since the unit is too small, only those substances which have relatively low molecular weight can
pass through the aqueous pores.

The upper limit of molecules transported by this system or mechanism transport is of 150 if its
spherical and 400 if it’s chain-like.

Ions of opposite charge of the pore lining – electrical charge

If drug molecules have electrical charge then it may affect the convective transport.

Hydrostatic pressure difference is due to the sifting of solvent so there are differences in pressure.

If fluid is viscous then movement will be much slower.

Drugs with low molecular weight can pass through pores

Examples of compounds absorbed by convective transport are small molecules like dextrose,
fructose, organic electrolyte, urea and water.
If a molecule has a charge then ion-pair transport is usually used. When the ionized drug is linked up
with oppositely charged ions, it forms an ion-pair. If they pair up then the charge will be cancelled.
Passive diffusion is supportive of ion-pair transport.

Organic anion will pair up with organic cation. It

will form a complex which causes neutralization of
their charges. It will then transverse through the
membrane by passive diffusion.

Once the ion-pair complex will be transported

inside then it will dissociate inside the
compartment so that the active drugs will bind to
the other complex to produce the desirable
effect.

Common examples of drugs transported via ion pair transport.

- This transport system Is responsible for the absorption of compounds which ionizes at all pH
values.
- Examples are quaternary ammonium, sulfonic acids, and propranolol (pairs with oleic acid).

Vesicular transport

- Has two processes, pinocytosis and phagocytosis (engulfment of large materials)

- A process of engulfing particles or dissolves materials by the cell.
- Phagocytosis has two processes which are endocytosis and exocytosis.

Pinocytosis

- It is the only transport mechanism where the drug compound does not have to be in
aqueous solution.
- It is called vesicular absorption, particulate absorption or corpuscular absorption.
- Absorption usually occurs from the lumen of the intestinal tract across the intestinal
epithelium into the lymphatic or venous capillaries.
Oil soluble vitamins

- Fat soluble vitamins, vitamins A, D, E, and K.

Uptake of nutrients

- Fatty acids, fats, and amino acids.

Vesicular transport is proposed to be the process for the absorption of orally administered sabin
polio vaccine.

Sabine polio vaccine uses the pinocytosis transport. Insulin also uses pinocytosis.