A Comparison of the Cardiovascular Actions of Daunomycin, Adriamycin and N-Acetyldaunomycin in Hamsters and Monkeys

The most consistent initial effects of adriamycin in hamsters and rhesus monkeys were bradycardia, hypotension, ventricular arrhythmias and respiratory depression, and large doses of N-acetyldaunomycin caused only minimal changes in all parameters.

Abstract

The most consistent initial effects of adriamycin (12.5–50.0 mg/kg) in hamsters and rhesus monkeys were bradycardia, hypotension, ventricular arrhythmias and respiratory depression. Daunomycin (50 mg/kg) produced ventricular arrhythmias at twice the dose of adriamycin. In both species large doses of N-acetyldaunomycin (200 mg/kg) caused only minimal changes in all parameters. Significant amounts of all 3 parent compounds were detected in hamster heart and lung tissues soon after injection. A relatively rapid conversion of both daunomycin and adriamycin to the aglycone was found, but a significantly higher percentage of the adriamycin aglycone was concentrated in these 2 tissues. In contrast, relatively little conversion of N-acetyldaunomycin was detected. Thus, the observed pharmacological actions may be related to differences in metabolism of the 3 compounds.