**4.3. Rectal administration**

This is the preferred route when the oral route is unsuitable because of nausea or if the drugs have objectionable taste or odor. This route also protects susceptible drugs from the biotransformation reactions in the liver. However, absorption by this route is often ir‐ regular and incomplete. Formulations such as suppositories or enemas are applied via rectal route.

Membranes are phospholipid bi-layers with interspersed integral and peripheral proteins which behave either as molecular 'gates' or 'pumps'. Molecular gates are non-specific. The intake of molecules into the cell depends on the charged groups in the pore and the size of molecule to be transported across the membrane. Molecular pumps, however, are highly specific and require energy for molecular transport. There are several mechanisms by which drugs traverse membranes to reach their intended target site and they include the following:

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This involves is the passage of polar but uncharged substances across water filled chan‐ nels in response to the concentration gradient. Simple diffusion is the mechanism of choice for water soluble drugs and those with low molecular weight such as the an aes‐ thetic nitrous oxide (44kD) and ethanol (46 KDa). The majority of lipid-soluble drugs permeate cell membranes by passive diffusion between the lipid molecules of the mem‐ brane. The permeation rate of a lipid soluble drug depends on the concentration of the drug, its lipid/water partition coefficient concentration of protons and the surface area of the absorbing membrane. The lipid/water partition coefficient of a drug is the principal

The higher the value of lipid/water partition coefficient of a drug, the more rapidly it will be absorbed and vice versa. The chemical force that causes lipid-soluble drugs to move readily across membranes is termed the hydrophobic force since water molecules repels the lipid-soluble drugs. In most cases, drug absorption can be enhanced by ab‐ sorption enhancers, such as fatty acids, phospholipids and muco-adhesive polymers. These compounds disrupt the lipid bilayer making it more permeable and also increase

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

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

**5.1. Simple diffusion**

factor determining its absorption.

the solubility of insoluble drugs.

**5.2. Facilitated diffusion**

**5.3. Active transport of drugs**

transport mechanism.

chemotherapy.

#### **4.4. Parenteral administration**

This mode of administration is also known as injection. It is generally more rapid and enables more accurate dose selection and predictable absorption. Parenteral routes include;
