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 leastsquares, 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. (Am J Vet Res 1997;58:511–515)