Concepts, properties, measurement, and computation of clearance rates of hormones and other substances in biological systems

A unified view of “clearance rates” for hormones and other substances in biological systems is developed and the overall concept is analyzed in the context of practical measurement schemes and the insights such measures can provide about a system. Several important properties and limitations of clearance rates, including plasma and “metabolic” clearance rates, are developed and analyzed. Among several new definitions presented, a new name, weighted-average plasma clearance rate (WAPCR), is suggested for a traditional measure of the plasma (or metabolic) clearance rate, i.e., the “dose divided by integral of the concentration” measure. This is done because the latter quantity represents a “plasma clearance rate” easy to interpret and apply only under special circumstances. It is shown that practical use of this so-called “model-independent” measure to determine the PCR is limited by the dynamical properties of the physiological system and experiment as well as the model chosen to represent it in the calculation. These situations, as well as other experiment design problems, are made explicit and their limitations are analyzed.