Pharmacokinetics of daunorubicinol in the rabbit: comparison with daunorubicin

The pharmacokinetics of daunorubicinol (DOL), the main metabolite of daunorubicin (DNR), was studied in rabbits and compared to that of daunorubicin after an 8 mg/kg dose. High-performance liquid chromatography was used to separate parent drug and metabolites. The plasma disappearance of DNR and DOL was triexponential. DOL was the major species detected in plasma and urine. Both drugs had large volumes of distribution. About 70% of DNR or DOL were bound to plasma proteins and mainly to albumin. Pharmacokinetic parameters of DOL obtained after injection of DOL were different from those calculated for DNR and those calculated for DOL after injection of DNR. The total urinary excretions of DNR or DOL were similar and amounted to 25% of the dose. No conjugates were identified in urine after enzymatic treatment. No fluorescent drug was identified in the feces. Anthracyclines were degraded in vitro in rabbit feces. The rabbit seems to be a good model for the study of anthracycline pharmacokinetics as our results in rabbits after DNR injection were similar to those in human studies.