Platinum pharmacokinetics in sulphur-crested cockatoos (Cacatua galerita) following single-dose cisplatin infusion

Objective To determine the pharmacokinetics of platinum (Pt) in cockatoos. Design A pharmacokinetic study of Pt, following a single IV infusion of cis platin, was done in six healthy sulphur-crested cockatoos (Cacatua galerita ). Procedure Birds were hydrated for 1 h before and 2 h after a 1-h cisplatin infusion (1 mg/kg, IV). Serial blood samples were collected for 96 h after initiation of the infusion and urine was collected for 2 h during the hydra tion period after cisplatin administration. Tissue samples from 10 organs w ere obtained at necropsy, 96 h after cisplatin infusion. Total Pt and filte rable Pt in plasma, urinary Pt and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacok inetic analysis was performed on the plasma and urine data. Results For total Pt and filterable Pt, the respective mean systemic cleara nces were 0.373 and 0.699 L/kg hourly, the steady stale volumes of distribu tion were 4.19 and 0.356 L/kg, and the mean residence times were 111 and 0. 512 h. Total plasma Pt displayed a bi-exponential decay profile with averag e half-lives of 0.398 and 79.0 h, while filterable Pt had a monoexponential decay with mean half-life of 0.413 h. The renal clearance during the 2-h p ostinfusion period was 0.167 L/kg hourly. The kidneys had the highest Pt ac cumulation (4.54 mu g/g DM). Conclusions and Clinical Relevance Cisplatin infusion in cockatoos was well tolerated and PI plasma concentrations were similar to those measured duri ng treatment of solid tumours in human patients. Despite anatomical, physio logical and biochemical differences among animal species, the pharmacokinet ic disposition of Pt in the cockatoo shares some features with the kinetics reported previously in rodents, dogs and human beings.