Pharmacokinetics considers the movement of drugs within the body and the way in which the body affects drugs with time. Once a drug has been administered by one of the routes previously described, it will then undergo four basic processes:

• Absorption
• Distribution
• Metabolism
• Excretion

The composition of the drug has an important influence on where the drug is absorbed, where the drug is distributed to, where and how effectively it is metabolised and finally how rapidly it is excreted. In addition, other factors such as the dose of drug, the client’s condition, and other therapeutic and environmental issues may also affect the effectiveness of these processes.

Each of these processes will now be considered in more detail.

Drug absorption

The process of absorption brings the drug from the site of administration into the circulatory or lymphatic system. Almost all drugs, other than those administered intravenously or some that are applied topically, must be absorbed before they can have an effect on the body. The term bioavailability is used to refer to the proportion of the administered drug that has reached the circulation, and that is available to have an effect. Drugs given intravenously may be considered to be 100% bioavailable as they are administered directly into the circulation and all of the drug may potentially cause an effect. Administration by other routes means that some of the drug molecules will be lost during absorption and distribution, and thus bioavailability is reduced.

Drugs administered orally are absorbed from the gastrointestinal tract, carried via the hepatic portal vein to the liver, and then undergo some metabolism by the liver before the drug has even had the opportunity to work. This removal of a drug by the liver, before the drug has become available for use, is called the first pass effect. Some drugs, when swallowed and absorbed, will be almost totally inactivated by the first pass effect eg. glyceryl trinitrate. The first pass effect can, however, be avoided if the drug is given by another route. Thus, glyceryl trinitrate, when administered sublingually or transdermally, avoids first pass metabolism by the liver and is able to cause a therapeutic effect.

Absorption following oral administration

For drugs given by all routes other than the intravenous route, several lipid cell membrane barriers will have to be passed before the drug reaches the circulation. Four major transport mechanisms exist to facilitate this process.

• Passive diffusion is the most important and most common. If the drug is present in the gastrointestinal tract in a greater concentration that it is in the bloodstream, then a concentration gradient is said to exist. The presence of the concentration gradient will carry the drug through the cell membrane and into the circulation. The drug will be transported until the concentrations of drug are equal on either side of the cell membrane. No energy is expended during this process.

• Facilitated diffusion allows low lipid soluble drugs to be transported across the cell membrane by combining with a carrier molecule. This also requires a concentration gradient and expends no energy.

• Active transport is only used by drugs which closely resemble natural body substances. This process works against a concentration gradient and requires a carrier molecule and energy to be expended.

• Pinocytosis or ‘cell-drinking’ is not a common method for absorbing drugs. It requires energy and involves the cell membrane invaginating and engulfing a fluid-filled vesicle or sac.

Factors affecting drug absorption from the gastrointestinal tract

A number of factors may influence the absorption of a drug from the gut. These include:

• Gut motility: If motility is increased and therefore transit time is reduced, there will be less time available for absorption of a drug. Hypomotility may increase the amount of drug absorbed if contact with the gut epithelium is prolonged.

• Gastric emptying: If increased, this will speed up drug absorption rate. If delayed, it will slow the delivery of drug to the intestine, therefore reducing the absorption rate.

• Surface area: The rate of drug absorption is greatest in the small intestine due to the large surface area provided by the villi.

• Gut pH: The pH of the gastrointestinal tract varies along its length. The changing environmental pH may have different effects on different drugs. Optimal absorption of a drug may be dependent on a specific pH.

• Blood flow: The small intestine has a very good blood supply which is one reason why most absorption occurs in this part of the gut. Faster absorption rates will occur in areas where blood supply is ample.

• Presence of food and fluid in the gastrointestinal tract: The presence of food in the gut may selectively increase or decrease drug absorption. For example, food increases the absorption of dicoumarol, whilst tetracycline absorption is reduced by the presence of dairy foods. Fluid taken with medication will aid dissolution of the drug and enhance its passage to the small intestine.

• Antacids: The presence of these in the gastrointestinal tract causes a change in environmental pH. They will increase absorption of basic drugs and decrease absorption of acidic ones.

• Drug composition: Various factors pertaining to the composition of the drug may affect the rate at which it is absorbed. For example, liquid preparations are more rapidly absorbed than solid ones, the presence of an enteric coating may slow absorption, and lipid-soluble drugs are rapidly absorbed.

Absorption following parenteral administration

Intradermal drugs diffuse slowly from the injection site into local capillaries, and the process is a little faster with drugs administered subcutaneously. Due to the rich supply of blood to muscles, absorption following an intramuscular injection is even quicker. The degree of tissue perfusion and condition of the injection site will influence the rate of drug absorption.

Absorption following topical administration

Drugs applied topically to the mucous membranes and skin are absorbed less than by oral and parenteral routes. Absorption is, however, increased if the skin is broken or if the area is covered with an occlusive dressing.