Residence Time Dispersion as a General Measure of Drug Distribution Kinetics: Estimation and Physiological Interpretation

Abstract

To evaluate distribution kinetics of drugs by the relative dispersion of disposition residence time and demonstrate its uses, interpretation and limitations. The relative dispersion was estimated from drug disposition data of inulin and digoxin fitted by three-exponential functions, and calculated from compartmental parameters published for fentanyl and alfentanil. An interpretation is given in terms of a lumped organs model and the distributional equilibration process in a noneliminating system. As a measure of the deviation from mono-exponential disposition (one-compartment behavior), the relative dispersion provides information on the distribution kinetics of drugs, i.e., diffusion-limited distribution or slow tissue binding, without assuming a specific structural model. It also defines the total distribution clearance which has a clear physical meaning. The residence time dispersion is a model-independent measure that can be used to characterize the distribution kinetics of drugs and to reveal the influence of disease states. It can be estimated with high precision from drug disposition data.