**5.2. Facilitated diffusion**

This type of diffusion is achieved by carrier molecules which combine with the drug in question to form complexes that can diffuse more rapidly across the membrane than free-drug could do alone. An example is the transport of nucleotide antimetabolites used in viral or cancer chemotherapy.

#### **5.3. Active transport of drugs**

This is the transport which is linked to a source of energy. Examples of specific active transport systems are the sodium pump, which maintains high potassium and low sodium ions inside the cell relative to the external medium and the calcium pump that maintains a high concen‐ tration of calcium inside the sarcoplasmic reticulum and a low concentration around the myofibrils. Active transport of drugs across membranes have been discovered and an example is the uptake of pentazocine (a narcotic antagonist) by leukocytes which is dependent upon energy supply (glucose) and can be inhibited by cyclazocine, which competes for the same transport mechanism.

#### **5.4. Pinocytosis and phagocytosis of drugs**

Proteins, bacterial toxins and drugs with high molecular weights, (1000 KDa or more) en‐ ter cells by means of pinocytosis and endocytosis. These substances finally enter the lyso‐ somal system.

Therefore organic acids such as barbiturates and acetyl salicylic acid (aspirin) have a higher

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http://dx.doi.org/10.5772/52014

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The degree of ionization of the drug when in the GIT or other body fluids is the main deter‐ minant of the amount of the drug found in an uncharged form and this depends upon the

If the pH of the fluid is low, the ionization of acidic drugs is less while the ionization of basic drugs will be high.When the pKa of a drug is equal to the pH of the surrounding fluid, there

Most of these barriers are typically the same systems that animals use for defense against invasion by foreign agents. These barriers include the skin, the GIT membranes, blood-brain

The superficial layer of the skin, stratum corneum is particularly impermeable to most drugs. The skin permeability for the drugs is enhanced by using a co-solvent system such as ethanol/ water which increases drug partition into the skin. The lipid domains of the buccal and nasal mucosa also restrict drug entry and the drugs which permeate are able to do so through passive diffusion using the hydrophilic trans-cellular spaces and direct permeation through the

The gap junctions between cells in different cell types within a tissue can form channels for the passage of drugs between epithelial, endothelial, and mesothelial cells of the same tissue. These channels comprise of a group of proteins known as connexin. Cells in different tissues are however connected by tight junctions and these can impair transport between cells in different tissues. The tight junctions are dynamic structures, which normally regulate the trafficking of nutrients, medium sized compounds between cells, and form a regulated barrier in spaces between cells. There is need therefore to use drug absorption enhancers such as bile salts and long chain acyl-carnitines which act as Ca2+chelatorsand disrupt the tight junctions thereby improving transport across the junctions. Tight junctions are shown in Figure 2.

absorption rate in the stomach.

RCOO-

RNH2+ H<sup>+</sup>

+ H<sup>+</sup>

**7. Types of tissue barriers to drugs**

Acidic drugs:

Ka

RCOOH⇌

Basic drugs:

NH3⇌ Ka

is 50% ionization.

barrier and placenta.

**7.1. Skin**

membrane.

**7.2. Tight junctions**

R –<sup>+</sup>

relation between pH of the fluid and the pKa of the drug:
