Pharmacokinetics

Pharmacokinetics, sometimes abbreviated as PK, (from Ancient Greek pharmakon "drug" and kinetikos "to do with motion") is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. The substances of interest include pharmaceutical agents, hormones, nutrients, and toxins. It attempts to discover the fate of a drug from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics describes how the body affects a specific drug after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the dose of administered drug. These may affect the absorption rate.

Pharmacokinetics is often studied in conjunction with pharmacodynamics, the study of a drug's pharmacological effect on the body.

A number of different models have been developed in order to simplify conceptualization of the many processes that take place in the interaction between an organism and a drug. One of these models, the multi-compartment model, gives the best approximation to reality, however, the complexity involved in using this type of model means that monocompartmental models and above all two compartmental models are the most frequently used. The various compartments that the model is divided into is commonly referred to as the ADME scheme (also referred to as LADME if liberation is included as a separate step from absorption):

• Liberation - the process of release of a drug from the pharmaceutical formulation.
• Absorption - the process of a substance entering the blood circulation.
• Distribution - the dispersion or dissemination of substances throughout the fluids and tissues of the body.
• Metabolization (or biotransformation, or inactivation) – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites.
• Excretion - the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.

The two phases of metabolism and excretion can also be grouped together under the title elimination. The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to fully comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipient, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug.

All these concepts can be represented through mathematical formulas that have a corresponding graphical representation. The use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics. Such as its acid dissociation constant (pKa), bioavailability and solubility, absorption capacity and distribution in the organism.

The model outputs for a drug can be used in industry (for example, in calculating bioequivalence when designing generic drugs) or in the clinical application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine as well.

http://en.wikipedia.org/wiki/Pharmacokinetics

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