Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding

Based on a generalized model, equations for calculating the mean residence time in the body at single dose (MRT) and at steady state (MRT(ss)), apparent steady-state volume of distribution (<(V)over cap (ss)>), and steady-state volume of distribution (V-ss) are derived for a drug exhibiting nonlinear protein binding. interrelationships between <(V)over cap (ss)> and V-ss as well as between MRT and MRT(ss) are also discussed and illustrated with simulated data. In addition, a method for estimating the central volume of distribution of the bound drug and the sum of the central volume of distribution of the unbound drug and the area under the first moment curve of distribution function for drugs with nonlinear protein binding is proposed and illustrated with both simulated and published data.