1992 Volume 4 Issue 1 Pages 7-14
Trimethadione (TMO) is regarded as a model drug for monitoring hepatic drug N-demethylation capacity in vivo. However, the isozyme of cytochrome P-450 that is responsible for N-demethylation of TMO has not been identified. Considering these facts, this study was designed to determine the Cytochrome P-450 species that participate in the TMO N-demethylation by employing several typical Inducers of cytochrome P-450 I, II, III and IV isozymes. Male Sprague Dawley (SD) rats were pretreated with typical cytochrome P-450 Inducers, such as 3-methylcholanthrene (3MC), isosaf role, ethanol, phenobarbital (PB), pregnenolone-16α-carbonitrile (PCN), dexamethasone (DEX), triacetyloleandomycin (TAO) and clofibrate, and the serum dimethadione (DMO) /TMO ratio was determined for evaluation of the effects of these Inducers on hepatic TMO metabolism. In clofibrate or PB pretreated rats, the serum DMO/TMO ratio was increased to approximately 2 or 4 times those in the control. In rats pretreated with other inducers however, the ratio did not change significantly compared to the controls. These results suggest that the cytochrome P-450 gene family (ies) induced by PB or clofibrate may be responsible for TMO metabolism in rats. On the other hand, it has also been suggested that the cytochrome P-450 I family that is induced by 3MC and isosafrole is not responsible for TMO metabolism in rats.
