Distribution of clomesone in mice.

The distribution of the novel alkylating agent clomesone [2-chloroethyl (methylsulfonyl)-methane sulfonate] has been studied in mice after iv administration of 35 mg/kg. In plasma, [14C]clomesone was eliminated in an apparent single phase with a half-life of 11 minutes. The elimination of total radioactivity occurred with an initial half-life of 51 minutes, and then in prolonged phase of undetermined length. At least two organic soluble metabolites were detectable in plasma. Highest tissue concentrations of radioactivity were in liver, kidney, and small intestines where, at most times of analysis, the levels were two to three times higher than those in plasma. The rate of elimination of radiolabel from spleen, lungs, brain, and muscle, which contained about equal concentrations of radioactivity at most times after dosing, paralleled the rate of loss from plasma. A major proportion of the radioactivity in tissues was bound to trichloracetic acid-precipitable macromolecules. Within 24 hours, 77.6% of the dose was recovered in urine. High-pressure liquid chromatographic analyses of 8-hour urine collections demonstrated that less than 2% of the dose was excreted unchanged. These results demonstrate that clomesone is rapidly eliminated from plasma and that it and/or its products become extensively bound to tissue components.