Enzyme induction by ethanol consumption affects the pharmacokinetics of inhaled m-xylene only at high levels of exposure.

The experimental study with rats was undertaken to verify the working hypothesis that enzyme induction caused by ethanol consumption affects the kinetics of m-xylene only at a high level of exposure. m-Xylene was administered to ethanol-treated rats either perorally (0.01, 0.02 or 0.1 ml/kg) or by inhalation (50, 100 or 500 ppm each for 6 h) and the concentration of m-xylene in the blood and the urinary excretion of a m-xylene metabolite (m-methyl hippuric acid or m-MHA) were measured with time. The ethanol consumption, which increased the in vitro m-xylene metabolism about 5-fold, had no effect on the metabolism of inhaled m-xylene in vivo until the exposure concentration was raised to 500 ppm. On the other hand, metabolism of m-xylene after oral administration was markedly enhanced at any dose by the consumption, as evidenced by a decrease in the blood concentration of m-xylene together with an increase in the urinary excretion of m-MHA. These findings indicate that enzyme induction does not affect the pharmacokinetics of inhaled m-xylene when its exposure concentration is low. This may be because the hepatic blood flow, rather than the enzyme activity, rate-limits the metabolism of m-xylene, which is highly metabolized in the liver.