Pharmacokinetics of anthracyclines in dogs: evidence for structure-related body distribution and reduction to their hydroxy metabolites.

The pharmacokinetic disposition of the anthracyclines, adriamycin (doxorubicin), daunorubicin, 4'-epi-adriamycin, carminomycin, and 4-demethoxy-daunorubicin, and the formation of their reduced C13 hydroxy metabolites were studied in dogs. The presence of a C14hydroxy group (adriamycin and 4'epi-adriamycin) drastically reduces the appearance of the C13 hydroxy metabolites in plasma. Substitution of the C4-H with C4-OH and C4-OCH3, in this rank order, decreases the area under the plasma concentration-time curves of the parent compounds and their C13 hydroxy metabolites.