Abstract
The experimental study with rats was undertaken to verify the working hypothesis that enzyme induction caused by ethanol consumption affects the kinetics ofm-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 ofm-xylene in the blood and the urinary excretion of am-xylene metabolite (m-methyl hippuric acid orm-MHA) were measured with time. The ethanol consumption, which increased the in vitrom-xylene metabolism about 5-fold, had no effect on the metabolism of inhaledm-xylene in vivo until the exposure concentration was raised to 500 ppm. On the other hand, metabolism ofm-xylene after oral administration was markedly enhanced at any dose by the consumption, as evidenced by a decrease in the blood concentration ofm-xylene together with an increase in the urinary excretion ofm-MHA. These findings indicate that enzyme induction does not affect the pharmacokinetics of inhaledm-xylene when its exposure concentration is low. This may be because the hepatic blood flow, rather than the enzyme activity, rate-limits the metabolism ofm-xylene, which is highly metabolized in the liver.
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Kaneko, T., Wang, PY. & Sato, A. Enzyme induction by ethanol consumption affects the pharmacokinetics of inhaledm-xylene only at high levels of exposure. Arch Toxicol 67, 473–477 (1993). https://doi.org/10.1007/BF01969918
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DOI: https://doi.org/10.1007/BF01969918