Abstract
Tissue distribution and pharmacokinetics of 3-t-[methyl-14C]butyl-4-hydroxyanisole was studied in male rats. 3-t-[methyl-14C]butyl-4-hydroxyanisole was administered by gavage at a single dose of 1.5 mmol/kg. Urine, feces, blood, and 20 major tissues were collected at 0.5, 1, 3, 6, 12, 16, 17, 18, 24, 48, 72, 168, and 240 hr after dosing and were analyzed for radioactivity. Almost all radioactivity was eliminated from rats in 48 hrs. Forty one per cent of the administered dose was recovered in urine, while feces accounted for 53%. At early time points radioactivity was mainly found in gastrointestinal tissues with concentrations remaining high up to 16-18 hr after administration indicating a slow absorption and elimination of the compound. The maximum concentration of radiolabel in kidney, liver, bladder, spleen, heart, pancreas, and brain was reached at 6 hr and remained up to 24 hr. The concentration of radioactivity in liver and kidney was approximately 10-fold higher than other tissues at the peak time of 16-18 hrs. Calculated absorption and elimination rate constants demonstrated slow uptake and clearance of label by many tissues. Covalent binding in eight representative tissues at 10 time points was also studied. Results indicate that binding increases slowly and exponentially with time reaching maximum levels at 12-24 hr in most of the tissues followed by a slow decline with time.