, Volume 24, Issue 4, pp 389-402

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

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Abstract

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 ( \(\hat V_{ss}\) ) and steady-state volume of distribution (V ss) are derived for a drug exhibiting nonlinear protein binding. Interrelationships between \(\hat V_{ss}\) andV ss as well as betweenMRT andMRT 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.