Distribution and elimination of melphalan in rats and monkeys and distribution in tumors of mice bearing L1210 or P388 leukemias sensitive and resistant to this agent.

Following iv injection, melphalan was eliminated monophasically from rat serum (half-life = 0.87 hour) and monkey serum (half-life = 1.9 hours) and in rat bile (half-life = 2.4 hours) and monkey urine (half-life = 1.3 hours). In rat bile and monkey urine, 2% and 20% of the dose, respectively, was excreted in 12 hours as unchanged melphalan. At each time of tissue assay (0.5-4 hours after injection), rat spleen contained less melphalan than serum, liver, or kidneys. The kidneys and bile of monkeys contained more melphalan that serum, liver, or spleen. Only a small amount of radioactivity from labeled melphalan appeared in the feces of monkeys. Melphalan reached higher concentrations in implants of P388 and L1210 leukemia cells sensitive to melphalan than in cell lines resistant to this drug. Furthermore, the amounts of radioactivity bound to macromolecules of the sensitive tumors were higher.