Abstract
There have been significant correlations between serum concentration ratios of 5, 5-dimethyl-2, 4-oxazolidinedione (Dimethadione, DMO) /trimethadione (TMO) after administration of TMO and hepatic microsomal cytochrome P-450 contents in rats with various treatments (CCl4 or phenobarbital). The pharmacokinetics of TMO and DMO, and the serum concentration ratio of DMO/TMO have been investigated in healthy volunteers after oral administration of 1mg/kg (N=4), 2mg/kg (N=6) and 4mg/kg (N=6) TMO, respectively. TMO and DMO concentrations in serum were determined by a gas-liquid chromatographic method. Serum disappearance of TMO was described by one compartment model. The T1/2, Kel, Vd and C1 of TMO and of DMO were shown to have almost the same values in 2mg/kg or 4mg/kg TMO administration. Correlation coefficient between DMO/TMO ratio in serum and time course after 1mg/kg, 2mg/kg and 4mg/kg TMO administration was found to be r=0.958, r=0.924 and r=0.938, respectively. These results indicate that the serum concentration ratio of DMO/TMO, especially at 2 or 4 h after 4mg/kg TMO administration orally, may be an index of hepatic drug-metabolizing capacity in human serum as well as in rats.
