Abstract
The effpcts of acute (24-, 48- or 72-hr) water deprivation on the disposition kinetics of trimethadione (TMO) and its only metabolite, dimethadione (DMO), and on the microsomal hepatic drug-oxidizing enzyme activities were investigated in male rats. The DMO/TMO ratios In the serum at 2 hr after intravenous administration of 100 mg/kg TMO were significantly decreased in 48- and 72-hr water-deprived rats, but in 24-hr water-deprived rats, the DMO/TMO ratios were not changed as compared to controls and food restrictions. In the 48- and 72-hr water-deprived rats, contents of cytochrome p-450 and activities of amino- pyrine N-demethylase were significantly decreased. On the other hand, activities of aniline hydroxylase in these rats were significantly increased as compared to controls and food restrictions. These results suggest that the effects of water deprivation on drug metabolism not only but also vary with the indicator substrate.
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