Estimation of ethanol first-pass effect in the perfused rat liver

Ethanol elimination was studied in the perfused rat liver. Perfusion was carried out in a single-pass fashion with hemoglobin-free Krebs-Ringer bicarbonate solution. A bolus ethanol dose (1.5, 3, 6, 12 mg/ml, 0.1 ml) was administered through portal vein from a sample loop exchanging a sample injector. Ethanol concentration-time curves of outflow were analyzed by statistical moment analysis. There was no significant difference in the normalized area under the curves [AUC/dose (D)] among doses. Mean transit time (MTT), however, was significantly changed. There was no correlation between AUD/D/g liver weight, or MTT, and D/g liver weight. This suggests that hepatic ethanol elimination exhibited a linear kinetics in the range of doses from 0.15 to 1.2 mg. The recovery ratio at all doses except 0.15 mg was similar to a value of 50%. The first-pass effect in the perfused liver calculated from the recovery ratio was estimated to be a mean value of 51.7% at doses of concentrations from 3 to 12 mg/ml. Our findings suggest that the hepatic saturation of ethanol can be reached by the continuous influx of low concentration of ethanol, rather than instantaneous influx with high ethanol levels.