Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur-crested cockatoos (Cacatua galerita)

The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma doxorubicinol concentrations were measured by HPLC. The pharmacokinetic parameters were estimated using a non-compartmental method. The mean (±SD) peak concentration was 8341 ± 3132 μg/L at 17.5 ± 5.0 min after the start of the infusion, and doxorubicinol concentrations declined biexponentially to 154.3 ± 34.5 μg/L, 40 min after the end of the infusion. Systemic clearance was 0.940 ± 0.473 L/h/kg, mean residence time was 0.165 ± 0.133 h, and steady-state volume of distribution was 0.123 ± 0.0526 L/kg. The terminal half-life was 0.660 ± 0.611 h. Detectible but unquantifiable concentrations of doxorubicinol were present in the plasma ultrafiltrate of two birds during the infusion, indicating very extensive plasma protein binding. Physiological, haematological and biochemical monitoring over 3 weeks showed that doxorubicinol at a single infused dose of 2 mg/kg caused no toxicities of major concern.