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There are various competing calculation methods for the drug accumulation ratio, yielding somewhat different results. A commonly used formula defines ''Rac'' as the ratio of the
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 determining the fate of substances administered ...
, the drug accumulation ratio (''Rac'') is the ratio of accumulation of a drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
under steady state
In systems theory, a system or a Process theory, process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those p ...
conditions (i.e., after repeated administration) as compared to a single dose. The higher the value, the more the drug accumulates in the body. An ''Rac'' of 1 means no accumulation.
Studies
The accumulation ratio of a specific drug in humans is determined byclinical studies
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
. According to a 2013 analysis, such studies are typically done with 10 to 20 subjects who are given one single dose followed by a washout phase of seven days (median
In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...
), and then seven to 14 repeated doses to reach steady state conditions. Blood samples are drawn 11 times (median) per subject to determine the blood concentration of the studied drug.
Calculation
There are various competing calculation methods for the drug accumulation ratio, yielding somewhat different results. A commonly used formula defines ''Rac'' as the ratio of the area under the curve
In mathematics, an integral assigns numbers to functions in a way that describes displacement, area, volume, and other concepts that arise by combining infinitesimal data. The process of finding integrals is called integration. Along with ...
(AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one singe dose:
:
where is the dosing interval, ''ss'' means ''steady state'' and 1 stands for a single-dose application.
Another definition sets ''Rac'' to the ratio of the average drug concentration during one day under steady state conditions to the concentration after a single dose.
Examples
References
{{Reflist Pharmacokinetic metrics