Modeling, analysis and experimental observations of fat volume properties in compartmental models for drug pharmacokinetics

Drug related dynamic uptake, clearance and anomalous diffusion patterns are dependent of biological tissue composition. Of particular importance is the fat volume, where drug trapping occurs in long term usage and related to lipophilic properties of drugs and non-homogeneous mixing. This paper introduces three probable drug pathways from fat volumes to augmented compartments, herein called trap volumes. In silico validation by using patient simulators with body mass index larger than 25. A non-homogeneous drug diffusion in biological tissue was considered using the partial-Caputo fractional-order compartmental model. To understand the effects in potential monitoring and sensing data information systems, an experiment has been proposed for in vitro impedance spectroscopy of fat samples. Variability with fat volume in observed data confirms the fractional-order characteristics that support theoretical model assumptions. A discussion section provides the implications for control of drug delivery systems. • Novel drug pathways in compartment models represent long-term distribution effects. • A partial-Caputo model captures non-homogeneous drug mixing properties. • In silico validation using digital patients agrees with clinical expectations. • In vitro impedance reveals fractional-order dynamics in adipose tissue storage.