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Volume of distribution and the effects of plasma protein and tissue
Volume of distribution and the effects of plasma protein and tissue

Distinguished Lecturer Series - Weizmann Institute of Science
Distinguished Lecturer Series - Weizmann Institute of Science



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Plateau principle

The plateau principle is a mathematical model or scientific law originally developed to explain the time course of drug action The principle has wide applicability in pharmacology, physiology, nutrition, biochemistry and system dynamics. It applies whenever a drug or nutrient is infused or ingested at a relatively constant rate and when a constant fraction is eliminated during each time interval. Under these conditions, any change in the rate of infusion leads to an exponential increase or decrease until a new level is achieved. This behavior is also called an approach to steady state because rather than causing an indefinite increase or decrease, a natural balance is achieved when the rate of infusion or production is balanced by the rate of loss.An especially important use of the plateau principle is to study the renewal of tissue constituents in the human and animal body. In adults, daily synthesis of tissue constituents is nearly constant, and most constituents are removed with a first order reaction rate. Applicability of the plateau principle was recognized during radiotracer studies of protein turnover in the 1940s by Rudolph Schoenheimer and David Rittenberg. Unlike the case with drugs, the initial amount of tissue or tissue protein is not zero because daily synthesis offsets daily elimination. In this case, the model is also said to approach a steady state with exponential or logarithmic kinetics. Constituents that change in this manner are said to have a biological half-life.A practical application of the plateau principle is that most people have experienced ""plateauing"" during regimens for weight management or training for sports. After a few weeks of progress, one seems unable to continue gaining in ability or losing weight. This outcome results from the same underlying quantitative model. This entry will describe the popular concepts as well as development of the plateau principle as a scientific, mathematical model.In the sciences, the broadest application of the plateau principle is creating realistic time signatures for change in kinetic models (see Mathematical model). One example of this principle is the long time required to effectively change human body composition. Theoretical studies have shown that many months of consistent physical training and food restriction are needed to bring about permanent weight stability in people who were previously overweight.
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