Key Points
- To compare the pharmacokinetics, metabolic pathways, and urinary excretion of doxorubicin and epidoxorubicin in cancer patients.
- Conducted a sequential crossover pharmacokinetic evaluation in eight patients (N=8) receiving 40 to 56 mg/m2 of both anthracyclines via bolus injection across two sequential cycles.
- Profiled parent drug and metabolite concentrations in plasma and urine across 48 hours to determine clearance, volume of distribution, AUC, and excretion.
- Epidoxorubicin (EPI) exhibited a smaller terminal half-life and volume of distribution, faster plasma clearance, and higher cumulative urinary recovery (10.5% vs 6.9% for DOX) over 48 hours.
- Glucuronide conjugation occurred uniquely with EPI (E-glu AUC exceeded Eol-glu), whereas doxorubicinol was the primary metabolite of DOX with twice the AUC of epirubicinol.
- Aglycone metabolites displayed secondary plasma concentration peaks between 2 and 12 hours post-injection, demonstrating enterohepatic circulation for derivatives lacking the daunosamine moiety.
Structured PICO
IInterventionEpidoxorubicin and doxorubicin 40 to 56 mg/m2 as a bolus injection in two sequential cycles
OOutcomePharmacokinetics of doxorubicin, epidoxorubicin, and their metabolites in plasma and urinesurrogate
Epidoxorubicin exhibits different pharmacokinetic properties than doxorubicin, including a shorter terminal half-life, smaller volume of distribution, and greater plasma clearance and urinary excretion.