title: Comparison of distributed and compartmental models of drug disposition: assessment of tissue uptake kinetics.
abstract: The utility of a circulatory three-compartment model for the assessment of tissue uptake kinetics is tested by comparison with the respective distributed models using pharmacokinetic data of rocuronium in patients These minimal physiologically based models have a common structure consisting of two subsystems representing the lung and the lumped systemic circulation, with two regions, the vascular and tissue space. The distributed models are based on either diffusion-limited tissue distribution, permeability-limited tissue uptake or the assumption of an empirical transit time density function. With a deviation in the estimate of the permeability-surface area product (PS) of about 18 %, the compartmental approach appears as a useful alternative on condition that a priori knowledge of cardiac output is included. It is also shown that the distribution clearance calculated from the parameters of a mammillary compartment model changes proportional to PS and can be used as an indirect measure of permeability-limited tissue uptake of drugs.
authors.affiliation: Department of Pharmacology, Martin Luther University Halle-Wittenberg, Halle, 06097, Germany. michael.weiss@medizin.uni-halle.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
mesh_terms: D000732:Androstanols / Q000097:blood / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics*; D000077123:Rocuronium; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium
keywords: Cardiac output; Circulatory compartment model; Distribution kinetics; Permeability-limited; Rocuronium