title: Fractal structure of the liver: effect on drug elimination.
abstract: Liver modeling in pharmacokinetics has been based on outflow curves of extracellular tracers obtained in single-pass perfused rat livers. These reference curves represent the hepatic transit time densities (TTD) of tracers. Since the fractal structure of the sinusoidal network implies a TTD with power-law tail, the question is whether the use of conventional empirical TTDs with exponential tail may lead to biased estimates of hepatic clearance. A simulation study using a novel TTD model that accounts for fractal heterogeneity of hepatic flow shows that the bias is less than about 5%. Using this approach to determine the influence of hepatic flow dispersion on drug extraction, only a minor effect was found. The results demonstrate that there is no need for specific fractal models of hepatic drug elimination.
authors.affiliation: Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. michael.weiss@medizin.uni-halle.de
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
mesh_terms: D000818:Animals; D017709:Fractals; D008658:Inactivation, Metabolic; D008099:Liver / Q000033:anatomy & histology* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010477:Perfusion / Q000379:methods; D010599:Pharmacokinetics; D051381:Rats