Pharmacokinetics: Definition, Phases, Drug Absorption and Drug Metabolism

It can be defined as the branch of pharmacology that studies the processes to which a drug is subjected through its passage through the body.

The pharmacokinetics can also be described simply as the study of “what the body does to the drug” and includes:

  •  The speed and extent to which drugs are absorbed in the body and distributed to body tissues.
  •  The speed and ways by which drugs are eliminated from the body by metabolism and excretion.
  •  The relationship between time and plasma drug concentration.

Understanding these processes is extremely important for prescribers because they form the basis on which the optimal dosage regimen is chosen and account for most of the interindividual variations in the response to drug therapy.

Pharmacokinetic phases

The main processes involved in pharmacokinetics are absorption, distribution and the two routes of drug elimination, metabolism and excretion. Together, they are sometimes known by the acronym ‘ADME’. Distribution, metabolism and excretion are sometimes collectively referred to as medication disposition.

Absorption is the process by which drugs enter the body. Given by any route other than intravenous, the drug molecules must cross the tissue membranes (for example, the cutaneous epithelium, the subcutaneous tissue, the intestinal endothelium, the capillary wall) to enter the blood.

Distribution is the process by which drugs move around the body. After entering the blood, the drug molecules must cross the capillary walls to enter the tissues, reach the cell membranes and enter the cells.

Metabolism is the process by which drugs are chemically altered to be sufficiently soluble in water for excretion in the urine or feces (through the biliary tract). Metabolism occurs in a variety of organs and body tissues, but mainly in the liver, intestinal wall, kidney and skin.

Excretion is the process by which drugs leave the body. Medications that are sufficiently soluble in water will be excreted without change in the urine. The fat-soluble drugs must be modified to water-soluble metabolites before their excretion through the kidney or into the intestine through the bile.

Drug absorption

Absorption is the process by which drug molecules gain access to the bloodstream from the site of drug administration. The speed of this process (the rate of absorption of the drug) and its completion (the degree of absorption of the drug) depend on the route of administration.

Administration routes can be considered in two categories:

Medications administered orally: are normally ingested before being absorbed in the stomach or small intestine, after which they enter the portal venous system and pass through the liver before entering the systemic circulation.

Some drugs introduced into the alimentary tract are absorbed directly into the systemic circulation without going through the liver (eg buccal, sublingual or rectal), thus avoiding the potential risks of gastric acid, food binding and metabolism by the intestinal wall or liver enzymes (first pass metabolism).

Parenteral : This includes any route that prevents absorption through the gastrointestinal tract, such as administration by injection, inhalation or application to the skin.

Absorption after an oral dose is a prolonged process, during which the drug molecules can be damaged (for example, denatured by gastric acid), sequestered (for example, linked to foods that impede absorption) or modified by the metabolism of first step.

As a consequence of all these risks, it is not surprising that absorption is often incomplete after oral administration. The proportion of a dose that arrives unscathed to the systemic circulation is known as the bioavailability of the drug.

Drug metabolism

Metabolism is the process by which drugs chemically change from a lipid-soluble form suitable for absorption and distribution to a more water-soluble form that is suitable for excretion. The process effectively eliminates the original medication.

The metabolism of drugs occurs in two phases:

Phase I: in which drug molecules are chemically altered (by oxidation, reduction or hydrolysis) to make them suitable for Phase II reactions or for excretion.

Oxidation is the most common form of a Phase 1 reaction and involves mainly members of the cytochrome family of membrane-bound enzymes in the smooth endoplasmic reticulum of liver cells.

Most Phase 1 metabolism products are pharmacologically inactive, although some retain activity to a greater or lesser degree, while others have activity that the original drug did not possess.

Phase II: in which the molecules of the Phase I metabolite (or, in some cases, unaltered drug) are combined with an endogenous substrate to form an inactive conjugate that is much more soluble in water than the Phase I metabolite.

Phase II reactions include synthesis of glucuronide or sulfate products, acetylation or methylation and conjugation with glutathione.

The rate of drug metabolism varies widely among individuals, influenced by genetic and environmental factors.

This is the main reason for the interindividual differences in the plasma concentration of some drugs after a standard dose, which leads to a wide variation in the drug response.