Pharmacokinetics of the absorption, distribution, and elimination of melphalan in the dog.

[14C]melphalan ([14C]L-PAM) was rapidly absorbed from the gut of dogs after oral dosing and reached a maximum concentration in the serum by 30 minutes. The disappearance of L-PAM (intact drug) from the serum was biphasic after iv administration, with half-lives of 14 and 66 minutes for the alpha and beta phases, respectively. The urinary excretion accounted for 44% of the total radioactivity and 25% appeared in the feces. Approximately 8% of the dose was excreted unchanged in the urine. Biliary excretion was rapid, with 11% of the dose being accounted for in the bile after 30 minutes; approximately 80% of these drug equivalents (materials containing radioactivity) was parent compound. Since large amounts of L-PAM appeared in the bile, the agent may prove to be active against cancers of the gall bladder, bile ducts, and duodenum.