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Hepatic Saturation Mechanism of Ethanol: Application of Mathematical Models to Ethanol Outflow Profiles in the Perfused Rat Liver
Author(s) -
Matsumoto Hiroshi,
Fukui Yuko
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01718.x
Subject(s) - ethanol , outflow , chemistry , mechanism (biology) , biochemistry , physics , quantum mechanics , meteorology
The saturation mechanism of hepatic ethanol (EtOH) elimination was studied in the perfused rat liver. EtOH outflow profiles after the instantaneous administration of 3 (mg/ml) × 0.4 (ml), 12 × 0.1, 24 × 0.1, and 3 × 0.1 mg (as a dose concentration × a volume) through the portal vein were analyzed by the statistical moment analysis and mathematical models (i.e., dispersion models). Results for 3 × 0.1 and 12 × 0.1 mg doses by moment analysis were similar. This demonstrated that the elimination exhibits linear kinetics. Recovery ratio and hepatic volume of distribution for 3 × 0.4 and 24 × 0.1 mg were larger than those for 3 × 0.1 and 12 × 0.1 mg doses and were similar. Kinetics after administration of 3 × 0.4 and 24 × 0.1 mg may be nonlinear. A difference in the relative dispersion ( CV 2 ) obtained by moment analysis between 3 × 0.4 and 24 × 0.1 mg doses indicated different properties of the nonlinear elimination kinetics. There were no differences in all the parameters in the one‐compartment dispersion model between 3 × 0.4 and 24 × 0.1 mg doses. In the two‐compartment dispersion model, there were differences in the blood volume ( V B ) and the forward partition rate constant ( K 12 ) between 3 × 0.4 and 24 × 0.1 mg ( p < 0.05), whereas the elimination rate constant ( k e ) and the dispersion number values for these doses were similar. These findings demonstrated that there is difference in the no‐equilibrium process between 3 × 0.4 and 24 × 0.1 mg doses. Therefore, we suggest that the continuous EtOH input into the liver causes the saturation of enzyme pathways and the change of the nonequilibrium process.