INFLUENCE OF 2 DIETS ON PHARMACOKINETIC PARAMETERS OF ALLOPURINOL ANDOXYPURINOL IN HEALTHY BEAGLES

Objectives-To determine whether diet influences the metabolism of IV a dministered allopurinol in healthy dogs. Animals-6 healthy female Beag les, 4.9 to 5.2 years old and weighing 9.6 to 11.5 kg. Procedures-Allo purinol was administered IV (10 mg/kg) while dogs consumed a 10.4% pro tein (dry weight), casein-based diet or a 31.4% (dry weight), meat-bas ed diet. After each dose, plasma samples were obtained at timed interv als, and concentrations of allopurinol and its active metabolite, oxyp urinol, were determined by high-performance liquid chromatography. An iterative, nonlinear regression analytical program was used to determi ne the weighted least-squares, best-fit curves for plasma allopurinol and oxypurinol concentration-time data. From these data, pharmacokinet ic parameters were calculated. Results- Pharmacokinetic parameters for allopurinol and oxypurinol were not different when comparing the effe ct of diet. Conclusion-There is no influence of diet on pharmacokineti c parameters of allopurinol or oxypurinol. Clinical Relevance-In contr ast to observations in human beings, allopurinol metabolism is not inf luenced by diet. Therefore, formation of xanthine-containing calculi i n dogs consuming a high-protein diet and receiving allopurinol is prob ably not attributable to alteration of allopurinol metabolism.