Influence of two diets on pharmacokinetic parameters of allopurinol and oxypurinol in healthy Beagles

Abstract

Objectives - To determine whether diet influences the metabolism of IV administered allopurinol in healthy dogs. Animals - 6 healthy female Beagles, 4.9 to 5.2 years old and weighing 9.6 to 11.5 kg. Procedures - Allopurinol was administered IV (10 mg/kg) while dogs consumed a 10.4% protein (dry weight), casein-based diet or a 31.4% (dry weight), meat-based diet. After each dose, plasma samples were obtained at timed intervals, and concentrations of allopurinol and its active metabolite, oxypurinol, were determined by high-performance liquid chromatography. An iterative, nonlinear regression analytical program was used to determine the weighted least-squares, best-fit curves for plasma allopurinol and oxypurinol concentration-time data. From these data, pharmacokinetic parameters were calculated. Results - Pharmacokinetic parameters for allopurinol and oxypurinol were not different when comparing the effect of diet. Conclusion - There is no influence of diet on pharmacokinetic parameters of allopurinol or oxypurinol. Clinical Relevance - In contrast to observations in human beings, allopurinol metabolism is not influenced by diet. Therefore, formation of xanthine-containing calculi in dogs consuming a high-protein diet and receiving allopurinol is probably not attributable to alteration of allopurinol metabolism.