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

Abstract

The purpose of this investigation is to determine the correlations 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 N-demethylase (r=0.999 at 1 h, p<0.01; r=0.994 at 2 h, p<0.01) and TMO N-demethylase (r=0.988 at 1 h, p<Tj.02; r=0.975 at 2 h, p<0.05), and aniline hydroxylase (r=0.993 at 1 h, p<0.01; r=0.979 at 2 h, p<0.01). These results indicate that the values of plasma DMO/TMO ratio determined at an appropriate time period following its administration would reflect 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 method for predicting hepatic drug-oxidizing capacity in humans.