Relationship between trimethadione metabolism and hepatic drug-oxidizing enzyme activities in different animal species.
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.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004114:Dimethadione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014293:Trimethadione / Q000378:metabolism*
D010080:Oxazoles; D003577:Cytochrome P-450 Enzyme System; D004114:Dimethadione; D014293:Trimethadione; D000983:Antipyrine