Interpretation and estimates of mean residence time with statistical moment theory.

The definitions of mean residence time of drug molecules in the body (MRT) from the literature are reviewed. A formal definition of MRT, based on excretion of drug molecules and amount of drug, a parameter which is independent of constancy of both clearance and volume of distribution, is introduced and compared to other existing definitions of MRTs, that is, MRT for the two-compartment model, MRT for the stochastic model, and MRT based on amount in the body. The inherent assumptions of the methods for determining the various MRTs are discussed. Published information on coefficients and constants (Collier) which describe a biexponential drug decay in the systemic circulation were utilized to illustrate the similarities and differences in MRTs. MRTs were calculated from theoretical relationships as well as estimated from simulated data based on equivalent conditions. The MRTs based on area under the moment curve/area under the curve (AUMC/AUC) for the two-compartment model and AUC/C(0) for the stochastic model assume a constancy in clearance and in volume of distribution, respectively.