Disposition and metabolic profile of a new antitumor agent: CL 216,942 (bisantrene) in laboratory animals.

A 14C-labeled antitumor drug, CL 216,942 (bisantrene), was administered iv at doses of 1-20 mg/kg to the monkey, dog, and rat. The serum concentration versus time profiles indicated at least a biphasic disappearance of the drug with long elimination half-lives of about 2-8 days in all three species. Total recoveries in the excreta collected through Day 7 were low (less than 50% of the administered dose), especially in the monkey and dog, with most of the drug found in the feces. Volumes of distribution in the central compartment as well as tissue distribution studies in all three species indicated a rapid uptake and significant concentration of the drug with long elimination half-lives in a deep compartment. The same organs and tissues (heart, liver, kidney, pancreas, spleen, lymph nodes, bone marrow, and most of the highly perfused glands) contained the highest drug concentrations in all three species. Metabolism studies indicated no evidence of significant biologic transformation of the drug in these species. In vitro studies by equilibrium dialysis indicated significant binding of the drug to DNA by intercalation.