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Effects of dose and dosing regimen on tissue distribution and elimination kinetics of [14C] dithiobiuret in rats.

[14C] Dithiobiuret (DTB)-derived radioactivity is eliminated by adult male rats with an approximate plasma half-life of 8-10 hr. About 65-75% of an i.p. dose appears in the urine within 24 hr after treatment and about 2-4% appears in the feces during the same time period. Less than 1% is recovered as [14C] carbon dioxide in expired air. The elimination kinetics for plasma and the % dose of DTB eliminated as the parent compound and metabolites in urine and feces, respectively, are the same for 1 mg/kg and 25 mg/kg acute treatments and for 1 mg/kg/day chronic treatment. Dose and dosing regimen dependent changes in tissue distribution are evident for most tissues with the thyroid gland, lung, stomach and fat being the most affected. Accumulation of DTB or its metabolites in the thyroid gland is greater than in any other tissue and is saturable at 25 mg/kg. The lung and stomach have a lower concentration of [14C] DTB equivalents than the thyroid, but they show the greatest relative increase in concentrations, about 5 fold, when [14C] DTB is administered chronically. Conversely, fat does not accumulate DTB-derived radioactivity during chronic dosing. These findings suggest that DTB metabolism is altered by changes in dose and dosing regimen.