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.
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.
D000818:Animals; D001711:Biotransformation; D003404:Creatinine / Q000652:urine; D005937:Glucaric Acid / Q000652:urine; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D010080:Oxazoles / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014293:Trimethadione / Q000097:blood / Q000378:metabolism* / Q000652:urine
D010080:Oxazoles; D004364:Pharmaceutical Preparations; D008748:Methylcholanthrene; D003404:Creatinine; D005937:Glucaric Acid; D014293:Trimethadione; D010634:Phenobarbital