Elimination kinetics of 2-butoxyethanol in the perfused rat liver--dose dependence and effect of ethanol.

The elimination kinetics of 2-butoxyethanol (ethylene glycol monobutyl ether, EGBE) were studied in the once-through isolated perfused rat liver system in the presence and absence of ethanol. Dose-dependent Michaelis-Menten kinetics in the elimination of EGBE were observed in the investigated concentration range. The apparent Michaelis constant range from 0.32 to 0.70 mM while the maximum elimination rate ranged from 0.63 to 1.4 mumol/min/g liver (parallel tube model) in six different experiments. The maximum intrinsic clearance varied between 0.7 and 2.0 ml/min/g liver. In the presence of 17.1 mM ethanol (0.1%) the extraction ratio of EGBE decreased from 0.44 to 0.11. The results support the hypothesis that EGBE is mainly metabolized via oxidation by alcohol dehydrogenase in the rat liver. The concentration dependence occurred at plausible in vivo doses.