In vitro formation of a toxic aglycone metabolite of 4-demethoxydaunorubicin in conditions that parallel the stomach.

4-Demethoxydaunorubicin is a new anthracycline anticancer drug administered orally to cancer patients. In vitro chemical stability has been studied in conditions that parallel the stomach (pH 1, dark, 37 degrees C) by HPLC. The drug was converted to its aglycone form at a rate of 3% (total starting amount) per hour. Thus, after only 3 to 4 hours significant aglycone formation had occurred (greater than 10%). The aglycone was detected to be present in patient urine in significant amount. Anthracycline aglycones lack cytotoxicity but retain toxic potential to host tissues. Formation in vivo in the stomach would result in a reduction in the therapeutic index of the drug.