Pharmacological and therapeutic efficacy of rubidazone in mice. Comparison with daunomycin and adriamycin

The pharmacological and therapeutic effects of rubidazone, the benzoyl-hydrazone chlorhydrate of daunorubicin (DNR), were compared with those of DNR and adriamycin (ADM) on an equimolar basis in an experimental animal system. The initial plasma levels of rubidazone fluorescence appeared to be higher than those of DNR and ADM but reached a similar level in 30 min. Tissue levels of these compounds were essentially similar except in the spleen and kidney where rubidazone and DNR levels were substantially higher than ADM. The patterns of in vitro uptake of rubidazone into L 1210 murine leukemic cells were of a mixed type as seen in DNR and ADM, namely, rapid initial uptake followed by gradual progressive increase. Decreased DNR fluorescence at later hours suggested an efflux of the compound. Rubidazone and DNR retention in L 1210 cells in vivo decreased rapidly in the initial hours and rubidazone displayed the lowest fluorescence retention of the 3 compounds. Therapeutic effects on mice bearing L 1210 leukemia were on the order of ADM > rubidazone ≧ DNR. The therapeutic effects of the 3 compounds were universally decreased in immunosuppressed mice bearing L 1210 leukemia. A slower rate of fluorescence decay from tumor cells during the first hours after drug administration appeared to be the only parameter correlated with the therapeutic superiority of ADM.