THE DISPOSITION AND METABOLISM OF 1,3,5-[U-C-14]TRIOXANE IN MALE WISTAR ALBINO RATS

The present study was designed to investigate 1,3,5-[U-C-14]trioxane ( TOX) distribution, excretion and metabolism. The experiments were perf ormed on male Wistar albino rats after a single administration of TOX at doses of 40 mg/kg and 400 mg/kg. The exhaled air proved to be the m ain route of C-14 elimination, mainly as (CO2)-C-14. During the first 12 h following the administration of 40 mg/kg of TOX the exhalation of (CO2)-C-14 was monophasic, with a half-life of 3.5 h. After the admin istration of 400 mg/kg, TOX was eliminated mainly as (CO2)-C-14 with t he exhaled air (77%) and unchanged TOX (8%). About 3% of C-14 was excr eted in the urine as unchanged 1,3,5-trioxane. With regards to TOX eli mination from blood plasma for the lower dose, a biphasic process was observed, with half-lives of 4.5 and 72 h. The amount of C-14 bound by the erythrocytes was minute compared with the amount in blood plasma. When the higher dose of TOX was administered the efficiency of C bind ing to the erythrocytes was found to be 10 times higher than the respe ctive value for blood plasma. Among the examined tissues the highest c oncentration of TOX-derived radioactivity was detected in the liver wh ile the lowest was in fat tissue and brain. A subsequent decay of radi oactivity occurred in the tissues. The results of the present study in dicate that TOX belongs to the group of compounds, which are rapidly e liminated from the organism; hence TOX should not be expected to accum ulate within the tissues. The data obtained confirm the assumed patter n of metabolic transformation, according to which 1,3,5-trioxane under goes enzymatic transformation to formaldehyde, with carbon dioxide and water being the final products.