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The purpose of this investigation is to correlate between trimethadione (TMO) metabolism and hepatic microsomal drug-oxidizing activities in different animal species (mouse, hamster, rat and rabbit). A good correlation was obtained between the plasma concentration ratio of 5,5-dimethyl-2,4-oxazolidinedione (DMO) to TMO and relative activities of aminopyrine (r = 0.999 at 1 h, p less than 0.01; r = 0.994 at 2 h, p less then 0.01) and TMO (r = 0.988 at 1 h, p less than 0.02; r = 0.975 at 2 h, p less than 0.05) N-demethylase, and aniline (r = 0.993 at 1 h, p less than 0.01; r = 0.979 at 2 h, p less than 0.01) hydroxylase. These results indicate that the values of plasma DMO/TMO ratio determined at an appropriate time period following its administration would be reflecting the degree of hepatic drug-oxidizing capacity in various experimental animal species. These findings thus suggest that in vivo TMO metabolism would be a useful drug for predicting hepatic drug-oxidizing capacity in humans.

Relationship between trimethadione metabolism and hepatic drug-oxidizing enzyme activities in different animal species.