Pharmacokinetics

Pharmacokinetics (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific substance after administration.

[1] The substances of interest include any chemical xenobiotic such as pharmaceutical drugs, pesticides, food additives, cosmetics, etc.

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 excipients, 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.

The following are the most commonly measured pharmacokinetic metrics:[5] The units of the dose in the table are expressed in moles (mol) and molar (M).

To express the metrics of the table in units of mass, instead of Amount of substance, simply replace 'mol' with 'g' and 'M' with 'g/L'.

In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination.

In practice, it is generally considered that once regular dosing of a drug is started, steady state is reached after 3 to 5 times its half-life.

[8] Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance.

Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine.

Noncompartmental methods are versatile in that they do not assume any specific model and generally produce accurate results acceptable for bioequivalence studies.

The number of time points available in order to perform a successful NCA analysis should be enough to cover the absorption, distribution and elimination phase to accurately characterize the drug.

However complicated and precise a model may be, it still does not truly represent reality despite the effort involved in obtaining various distribution values for a drug.

The choice of model therefore comes down to deciding which one offers the lowest margin of error for the drug involved.

Other tissues, such as the brain, can occupy a variable position depending on a drug's ability to cross the barrier that separates the organ from the blood supply.

The most common situation is that elimination occurs in the central compartment as the liver and kidneys are organs with a good blood supply.

If we label the drug's volume of distribution within the organism VdF and its volume of distribution in a tissue VdT the former will be described by an equation that takes into account all the tissues that act in different ways, that is: This represents the multi-compartment model with a number of curves that express complicated equations in order to obtain an overall curve.

Once a drug's bioavailability has been established it is possible to calculate the changes that need to be made to its dosage in order to reach the required blood plasma levels.

Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma.

[13][14] Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often plasma or urine) and the need for high sensitivity to observe concentrations after a low dose and a long time period.

[15][16][17] There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation.

[18] Recent studies show that Secondary electrospray ionization (SESI-MS) can be used in drug monitoring, presenting the advantage of avoiding animal sacrifice.

[20][21][22] Certain patient demographic, pathophysiological, and therapeutical features, such as body weight, excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships and can explain variability in exposures.

An advantage of population pharmacokinetic modelling is its ability to analyse sparse data sets (sometimes only one concentration measurement per patient is available).

The drug's therapeutic properties were initially demonstrated, but it was almost never used after it was found to cause nephrotoxicity in a number of patients.

Clinical monitoring is usually carried out by determination of plasma concentrations as this data is usually the easiest to obtain and the most reliable.

[25][26] Ecotoxicology is studied in pharmacokinetics due to the substances responsible for harming the environment such as pesticides can get into the bodies of living organisms.

The health effects of these chemicals is thus subject to research and safety trials by government or international agencies such as the EPA or WHO.

[27][28] How long these chemicals stay in the body, the lethal dose and other factors are the main focus of Ecotoxicology.