Tanaka E, Kinoshita H, Yoshida T, Kuroiwa Y
J Pharmacobiodyn. 1982 Mar;5(3):162-71. doi: 10.1248/bpb1978.5.162.
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.
为了确定大鼠血浆和尿液中三甲双酮（TMO）及其代谢产物5,5-二甲基-2,4-恶唑烷二酮（DMO）的浓度是否为药物代谢能力的有用指标，进行了以下实验。在给予TMO后，测量苯巴比妥（PB）或3-甲基胆蒽（3-MC）预处理大鼠的血浆TMO和DMO浓度。在PB预处理的大鼠中，消除速率常数（Kel）与血浆DMO/TMO比值之间存在良好的相关性；1小时时r = 0.991，2小时时r = 0.967。然而，在3-MC预处理的大鼠中没有良好的相关性（1小时时r = 0.780，2小时时r = 0.720）。给予TMO后，PB和3-MC预处理大鼠在24小时尿液中的TMO和DMO排泄没有显著差异。这些实验与先前的研究结果表明，PB预处理大鼠血浆中TMO和DMO的浓度而非尿液中的浓度可能是药物代谢能力的有用指标。
