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 resid ence 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 di scussed and illustrated with simulated data. In addition, a method for estimating the central volume of distribution of the bound drug and t he sum of the central volume of distribution of the unbound drug and t he area under the first moment curve of distribution function for drug s with nonlinear protein binding is proposed and illustrated with both simulated and published data.