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Doxorubicin pharmacokinetics following a single‐dose infusion to sulphur‐crested cockatoos ( Cacatua galerita )
Author(s) -
GILBERT CM,
FILIPPICH LJ,
CHARLES BG
Publication year - 2004
Publication title -
australian veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.382
H-Index - 59
eISSN - 1751-0813
pISSN - 0005-0423
DOI - 10.1111/j.1751-0813.2004.tb13246.x
Subject(s) - pharmacokinetics , doxorubicin , volume of distribution , cmax , pharmacology , saline , metabolite , medicine , chemistry , chromatography , anesthesia , chemotherapy
Objective To determine the pharmacokinetics of doxorubicin in sulphur‐crested cockatoos, so that its use in clinical studies in birds can be considered. Design A pharmacokinetic study of doxorubicin, following a single intravenous (IV) infusion over 20 min, was performed in four healthy sulphur‐crested cockatoos ( Cacatua galerita ). Procedure Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused IV over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse‐phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL Established non‐parametric methods were used for the analysis of plasma doxorubicin data. Results During the infusion the mean ± SD for the C max of doxorubicin was 4037 ± 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (β‐phase) half‐life was 41.4 ± 18.5 min, the systemic clearance (Cl) was 45.7 ± 18.0 mL//min/kg, the mean residence time (MRT) was 4.8 ± 1.4 min, and the volume of distribution at steady state (V SS ) was 238 ± 131 mL/kg. The extrapolated area under the curve (AUC 0‐ ∝) was 950 ± 677 ng/mL.h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate‐limited pharmacokinetics of doxorubicinol. Conclusions and clinical relevance Doxorubicin infusion in sulphur‐crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half‐life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.