Pharmacokinetic, toxicologic, and chemotherapeutic properties of detorubicin in mice: a comparative study with daunorubicin and adriamycin.

We have studied the stability, pharmacology, toxicology, and therapeutic activity in mice of detorubicin, a new semisynthetic derivative of daunorubicin. In vitro, detorubicin remains stable under acidic conditions while it is very quickly hydrolyzed into Adriamycin under neutral pH conditions. In vivo, the hydrolysis of detorubicin into Adriamycin occurs in the bloodstream a few minutes after iv injection. The tissue distribution of detorubicin in mice is, however, very distinct from that observed after administration of Adriamycin and daunorubicin. The therapeutic effect of detorubicin on the sc implanted L1210 leukemia is superior to that of daunorubicin and at least equal to that of Adriamycin. Detorubicin can thus be considered a prodrug of Adriamycin with very distinct pharmacokinetic and perhaps therapeutic properties.