Commentary: using the convection-dispersion model and transit time density functions in the analysis of organ distribution kinetics.
The convection-dispersion model and its extended form have been used to describe solute disposition in organs and to predict hepatic availabilities. A range of empirical transit-time density functions has also been used for a similar purpose. The use of the dispersion model with mixed boundary conditions and transit-time density functions has been queried recently by Hisaka and Sugiyama in this journal. We suggest that, consistent with soil science and chemical engineering literature, the mixed boundary conditions are appropriate providing concentrations are defined in terms of flux to ensure continuity at the boundaries and mass balance. It is suggested that the use of the inverse Gaussian or other functions as empirical transit-time densities is independent of any boundary condition consideration. The mixed boundary condition solutions of the convection-dispersion model are the easiest to use when linear kinetics applies. In contrast, the closed conditions are easier to apply in a numerical analysis of nonlinear disposition of solutes in organs. We therefore argue that the use of hepatic elimination models should be based on pragmatic considerations, giving emphasis to using the simplest or easiest solution that will give a sufficiently accurate prediction of hepatic pharmacokinetics for a particular application.
Roberts
M S
MS
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia. M.Roberts@mailbox.uq.edu.au
Anissimov
Y G
YG
Weiss
M
M
D000465:Algorithms; D000818:Animals; D018481:Convection; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution