Disposition of indicine N-oxide in mice and monkeys

The disposition of tritium-labeled indicine N-oxide (INO) was evaluated in mice and rhesus monkeys. Disappearance of INO from the serum of BDF1 mice given iv doses of 100 or 500 mg/kg occurred with an initial half-life of about 11 mins followed by a second phase greater than 100 mins. At 2 hrs after iv injection of mice, the highest concentrations of INO were present in kidney, liver, and intestine. In CDF1 mice bearing P388 leukemia cells and injected ip with a dose of 500 mg/kg, INO was found, in equal concentrations, in cells of the parent line, which is resistant to INO, and in cells of a line resistant to cyclophosphamide but sensitive to INO. Serum levels of INO in these mice decreased with an initial half-life of about 20 mins. For monkeys given iv doses of 24, 2.4 of 0.24 mg/kg, INO disappeared from the serum in three phases, with average half-lives of 3, 32, and 180 mins, respectively. Half-lives for the two observed phases of urinary excretion were 40 and 240 mins. In 24 hrs, both mice and monkeys excreted greater than 80% of the doses unchanged.