Compositions and methods of reducing tissue levels of drugs when given as orotate derivatives

摘要

This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. These orotate derivatives are equally efficacious in inhibiting the SCCAKI-1 kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HCl suggests a reduction in toxicity induced by free radical generation by the anthracyclines.