The term pharmacokinetics covers all the processes to which drugs are subject in the body. This involves the action of the body on the pharmaceuticals. In contrast, the influence of the active ingredients on the organism is referred to as pharmacodynamics.
What is pharmacokinetics?
The term pharmacokinetics covers all the processes to which the drugs are subject in the body. This involves the action of the body on the pharmaceuticals. Pharmacokinetics describes the release, absorption, distribution, biochemical metabolization, and excretion of drugs in the body. In short form, this overall process is referred to as LADME. The word LADME is composed of the first letters of the English terms for release (liberation), absorption (absorption), distribution (distribution), metabolism (metabolism) and excretion (excretion). The terms pharmacokinetics and pharmacodynamics should not be confused. The description of pharmacokinetics is not concerned with the mechanism of action of the pharmaceutical, but with its change under the influence of the body. Conversely, the mechanism of action of the drug on the target organ is described under the term pharmacodynamics. Pharmacokinetics was founded in 1953 by the German pediatrician Friedrich Hartmut Dost as a result of his realization that dose recommendations of drugs for adults and children must be determined according to different laws.
Function, effect, and goals
The five phases of pharmacokinetics are further divided into the invasion and evasion phases. The invasion phase includes release, absorption, and distribution. In this phase, the drug is delivered to the organism. The metabolism and excretion of the drug belong to the evasion phase (removal from the body). Release (liberation) of the active substance becomes necessary if the drug is not already in dissolved form. Liberation is the rate-determining step in the entire process. Therefore, the dosage form of the drug must be adapted to the desired speed of its efficacy. Since rapid efficacy is desired for acute pain, fast-release tablets or effervescent tablets are administered here. However, when symptoms such as nausea and vomiting are also present, administration of suppositories is more appropriate despite slower drug release. Special challenges exist when modified drug delivery is necessary. This is the case, for example, when the active ingredient would be destroyed by gastric acid. In this case, its release may only occur after the tablet or capsule has passed through the stomach. This can be achieved by appropriately formulating the tablet with an acid-resistant protective layer. The protective layer is then dissolved in the small intestine. Furthermore, so-called sustained-release tablets can ensure a delayed release of the active ingredient in order to extend the dosing interval. Some therapeutic systems rely on controlled release of the active ingredient over a long period of time. The second step is the absorption of the active ingredient into the bloodstream. If the drug is administered in liquid and dissolved form, the previous step of release is omitted. The absorption process can occur via various mechanisms, such as passive diffusion through cell membranes, carrier-mediated diffusion, active transport, or phagocytosis. In this process, many physical or chemical factors influence resorption. For example, the size and blood flow of the resorption surface as well as the contact time with it play a major role. A shortened contact can, for example, result from an excessively rapid intestinal passage during diarrhea, in which case the efficacy of the drug is greatly reduced. In the third step, the active ingredient circulates in the blood and is thus distributed throughout the body. This is also how it reaches the target organ. Distribution is again dependent on many parameters such as solubility, chemical structure or binding capacity to plasma proteins. Furthermore, the structure of the organs, the pH value or the penetrability of the membranes also play a role. In the fourth step, the so-called metabolism of the active substance occurs mainly in the liver. It is first functionalized and then hydrophilized in a further step. During functionalization, oxidation or reduction reactions or hydrolysis take place.The active ingredient either becomes ineffective or even increases its effect. In some cases, toxins can also be formed during metabolization. During hydrophilization, the drug acquires a functional group that makes it water-soluble. Thus, the reaction product can then be excreted in the urine in the fifth step of pharmacokinetics.
Risks, side effects, and hazards
Each phase of a drug’s pharmacokinetics also holds risks for the organism. Even the phase of release determines the effectiveness of the drug’s action. In the worst case, the drug may remain completely ineffective if the dosage form is unsuitable. Furthermore, the pharmaceutical industry also faces the challenge of formulating the tablets or capsules in such a way that they develop their effect at the right time or are effective over a longer period of time. The absorption of the active ingredients can also be disturbed by intestinal diseases. In these cases, other dosage forms must be found for the drugs. The distribution of drugs in the body can sometimes lead to accumulation in certain organs. Fat-soluble drugs in particular are stored in fatty tissue and can often only be eliminated from the body very slowly. It is during the metabolization of the active ingredients that the greatest problems can occur. The chemically altered substances often have other effects on the organism. Many side effects result from specific degradation products of drugs. Sometimes the metabolization even leads to an increase in the effect. If several drugs are taken at the same time, metabolization may occur at different rates. The slower metabolized drugs accumulate with enhancement of their effect. Thus, pharmacokinetics can explain many drug side effects and cross-reactions of different drugs.
