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To determine whether concentrations of trimethadione (TMO) and its metabolite 5,5-dimethyl-2,4-oxazolidinedione (DMO) in plasma as well as in urine of rats are useful indicator of drug-metabolizing capacity or not, the following experiments were carried out. Plasma TMO and DMO concentrations were measured in phenobarbital (PB) or 3-methylcholanthrene (3-MC)-pretreated rats following the administration of TMO. In PB-pretreated rats, there was a good correlation between elimination rate constant (Kel and plasma DMO/TMO ratio; r = 0.991 at 1 h, r = 0.967 at 2 h). However, there was no good correlation in 3-MC-pretreated rats (r = 0.780 at 1 h, r = 0.720 at 2 h). TMO and DMO excretion in PB and 3-MC pretreated rats following the administration of TMO were not significantly different in 24-h urine. These experiments, together with the previous findings, indicate that concentrations of TMO and DMO in plasma, but not in urine, in PB-pretreated rats may be a useful indicator of drug-metabolizing capacity.

journal of pharmacobio-dynamics

Studies on the trimethadione metabolism as a tool for the assessment of drug-metabolizing capacity using plasma and urine of rats pretreated with phenobarbital and 3-methylcholanthrene.