Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12834
Title: Models of hepatic elimination: implications from studies of the simultaneous elimination of taurocholate and diazepam by isolated rat liver under varying conditions of binding.
Authors: Ching, M S;Morgan, Denis J;Smallwood, R A
Affiliation: University of Melbourne Department of Medicine, Austin Hospital, Victoria, Australia.
Issue Date: 1-Sep-1989
Citation: The Journal of Pharmacology and Experimental Therapeutics; 250(3): 1048-54
Abstract: Various kinetic models have been developed to describe the elimination of substances by the liver, but there is no agreement about which model is the most appropriate, as experimental evaluation is incomplete and results conflict. We have shown previously that hepatic elimination of taurocholate is best described by models that embody a high degree of sinusoidal heterogeneity or mixing, whereas another study showed that elimination of diazepam is best described by models that embody a low degree of sinusoidal heterogeneity or mixing. To investigate this discrepancy we examined, in the isolated perfused rat liver, the simultaneous elimination of taurocholate and diazepam. The effect on hepatic availability of varying unbound fraction (fu) in a single pass, steady-state system was studied in six experiments for taurocholate (fu, 0.066-0.966) and diazepam (fu, 0.051-0.675) by varying perfusate albumin concentration (0-60 g l-1). As before, elimination of taurocholate was best described by models that embody a high degree of sinusoidal heterogeneity or mixing (i.e., venous equilibrium model, dispersion model with dispersion number = infinity). Diazepam elimination was best described by models that embody a low degree of sinusoidal heterogeneity or mixing (undistributed sinusoidal model, dispersion model with low dispersion number = 1.04). A third model, a distributed model incorporating heterogeneity of sinusoidal blood flows and intrinsic clearances, fitted the data for both taurocholate and diazepam. The fitted coefficients of variation of both flow and intrinsic clearance among the sinusoids were large for taurocholate (176 and 164, respectively), but for diazepam blood flow was large (200) whereas that for intrinsic clearance was small (0.807).(ABSTRACT TRUNCATED AT 250 WORDS)
Internal ID Number: 2778709
URI: http://ahro.austin.org.au/austinjspui/handle/1/12834
URL: http://www.ncbi.nlm.nih.gov/pubmed/2778709
Type: Journal Article
Subjects: Animals
Diazepam.metabolism
In Vitro Techniques
Kinetics
Liver.metabolism
Metabolic Clearance Rate
Rats
Rats, Inbred Strains
Taurocholic Acid.metabolism
Appears in Collections:Journal articles

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