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Hepatic transport kinetics: effect of anatomic and metabolic heterogeneity on estimates of the average transfer coefficients.

In the accompanying paper we explore the analysis of solute disappearance curves using conventional linear assumptions. In this study we extend the analysis to examine the possibility of using the same model to recover the average kinetic parameters when the liver lobule displays anatomic and metabolic heterogeneity. The results show that the linear model can be used to recover good estimates of the average transfer coefficients, even though the kinetic parameters that govern uptake, efflux, and excretion are nonlinear functions of sinusoidal length. The inhomogeneities that we have examined include a variable surface-to-volume ratio of the sinusoids, saturation kinetics at the canalicular face of the liver cells, and a lobular profile of metabolizing enzyme or excretory carrier units per unit length of sinusoid.