Disposition kinetics of aspirin in female New Zealand white rabbits

Abstract

Limited information exists on the disposition of aspirin in rabbits. Such information is of value not only for treatment but also for development of experimental protocols with human applications. We evaluated the pharmacokinetics of aspirin at different doses by monitoring serum concentrations of the major metabolite, salicylic acid (SA). Four groups of six female New Zealand white rabbits received 2.5, 10, 20, or 50 mg of aspirin/kg of body weight. Aspirin was given once daily via the oral-gastric route, and blood samples were obtained after the third dose. Samples were collected before the last dose, then at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after dosing. Analysis of SA was completed by a validated assay on a high-performance liquid chromatography system. Mean maximal serum SA concentration was 7.54, 22.65, 43.2, and 70 micrograms/ml for the 2.5, 10, 20, and 50 mg/kg doses respectively. The total systemic clearance of SA was not altered by increasing doses of aspirin, but statistically significant differences were noted in the volume of distribution. The SA elimination half-life also increased proportionally with the aspirin dose. Bleeding tendency was associated with the highest dose of aspirin. Results of this study suggest that the 20 and 50 mg/kg dosages produced serum SA concentrations that simulate those observed in humans after 600-mg and 1.2-g aspirin doses respectively.