DRUG TRANSPORT MECHANISMS

Absorption of drugs is the process of uptake of the compound from the site of administration into the
systemic circulation. A prerequisite for absorption is that the drug be in aqueous solution.

Drugs are transported across a cell membrane, which is a semipermeable structure composed of lipid and
proteins.

Drug transport principles are summarized below:

1. Drug absorption requires that drug to be transported across various cell membranes
2. Drug molecules may enter the blood stream and be transported to the tissues and organs of the
body
3. Drug molecules may cross additional membranes to enter the cells
4. Drug molecules may also cross intracellular membranes such as nuclear membranes, endoplasmic
reticulum to reach the site of action.
5. Cell membranes are semipermeable membrane structures composed of lipids and proteins.
6. Drugs bound to proteins and macromolecules do not easily cross cell membranes
7. Non-polar lipid soluble drugs traverse cell membranes more easily than do ionic or polar water
soluble drugs
8. Low molecular weight drugs diffuse across a cell membrane more easily than do high molecular
weight drugs.

DRUG TRANSPORT MECHANISMS

1. Passive diffusion and partitioning
 Occurs within the cytoplasm or in the interstitial fluid.
 It is the transport of drugs through a semipermeable membrane.
 Most drugs cross cell membranes by passive diffusion, moving from an area of high
concentration (C1) to an area of lower concentration (C2) according to Fick’s Law of
diffusion.

Passive drug transport across cell membranes involves the successive partitioning of a solute between
aqueous and lipid phases as well as diffusion within respective phases. Modifying Fick’s Law of diffusion
to accommodate the partitioning of drugs gives the following equation:

dQ/dt = DAK/h (C1 – C2)

Where:
dQ/dt = is the rate of drug diffusion
D = is the diffusion coefficient for the drug
A = surface area across which transfer occurs
K = oil/water partition coefficient of the drug
h = is the thickness of the membrane
(C1 – C2) = difference between the drug concentration at the absorption site and in the plasma respectively

2. Carrier-mediated transport
A. Active transport mechanism of drug across a membrane is a carrier mediated process that has the
following characteristics:
a. The drug moves against a concentration gradient.
b. The process requires energy in the form of ATP.
c. The carrier may be selective for certain types of drugs that resemble natural substrates or
metabolites that are normally actively transported.
d. The carrier system may be saturated at high drug concentration.
e. The process may be competitive (e.g., drugs with the same structure may compete for the
same carrier.
B. Facilitated diffusion
For facilitated transport, drug molecules must be in aqueous solution at the absorption site. The
mechanism is the same as for active transport with the only difference that the transport does not
proceed against a concentration gradient.
This is also a carrier-mediated and does not require energy. Below is a picture that shows the 3
processes.

3. Paracellular transport
Drug transport across tight (narrow) junctions between cells or transendothelial channels of cells.
It involves both diffusion and convective (bulk) flow of water and accompanying water-soluble
drug molecules through paracellular channels.
Connective Transport (Pore Transport) – in convective transport drug molecules dissolved in
aqueous medium at the absorption site moves along with the solvent (shifting of the solvent)
through the pore. Ions (which have opposite charges of the pore lining) as well as neutral
molecules may pass through the pore.
4. Vesicular Transport
Transport of material out of a cell and into a cell involving vesicles are either formed
intracellularly and fuse with the plasma
membrane (exocytosis), or are formed by the plasma membrane, separate and fuse intracellularly
with lysosomes (endocytosis).

Endocytosis is the uptake of extracellular material, exogenous molecules, macromolecules, into a

cell by invagination of the plasmalemma and, vesicular formation. Endocytosis is subdivided
into:
a. Phagocytosis (cell eating) to describe internalization of particulate matter visible under the
light microscope.
b. Pinocytosis (cell drinking) to describe uptake of very small solid particles (not visible under
the light microscope), solutes and fluid.
The vesicles internally fuse with lysosomes releasing the entrapped content.

Endocytosis is the only transport mechanism in which a drug or compound does not have to be
in aqueous solution in order to be absorbed.