Dose-independent pharmacokinetics of trimethadione and its metabolite in rats.
The aim of the present study was to examine the dose-independent kinetics of trimethadione (1) and its only metabolite dimethadione, 5,5-dimethyl-2,4-oxazolidinedione (2), after oral administration of 1-, 2-, and 4-mg/kg doses of 1 to rats. Pharmacokinetic parameters determined after oral administration of these doses showed that the half-life (t 1/2), metabolic clearance (CL), and apparent volume of distribution (Vd) were not significantly changed by increasing or decreasing the dose of 1, whereas there was a linear relationship between the dose of 1 and the area under the curve (AUC) (1, r = 0.912; 2, r = 0.976) or the maximum serum concentration (Cmax) (1, r = 0.990; 2, r = 0.980). The ratios of 2 to 1 at 1 and 2 h after oral administration of 1 were not significantly different. These experiments indicate that serum pharmacokinetic behavior of 1 and 2 1 or 2 h after oral administration of 1 to the rat is independent of the dose of 1 in the 1-4 mg/kg range.
D000818:Animals; D002849:Chromatography, Gas; D004114:Dimethadione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D010080:Oxazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014293:Trimethadione / Q000378:metabolism*
D010080:Oxazoles; D004114:Dimethadione; D014293:Trimethadione