Comparison of pharmacokinetic and pharmacodynamic properties of allopurinol and benzbromarone in a quail model of hyperuricemia

在鹌鹑高尿酸血症模型中比较别嘌醇和苯溴马隆的药代动力学和药效学特性

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Abstract

IMPORTANCE: Hyperuricemia (HUA) is a major metabolic disorder in poultry, leading to gout and kidney damage, which affects farm productivity. Accordingly, understanding the pharmacodynamics (PD) and pharmacokinetics (PK) of uric acid-lowering drugs is essential for improving the treatment strategies in poultry. OBJECTIVE: This study examined the PD and PK characteristics of allopurinol and benzbromarone, two uric acid-lowering drugs, in a quail model of HUA. METHODS: A hyperuricemic quail model was established using a high-purine diet. Allopurinol and benzbromarone were administered orally. Blood samples were taken and analyzed for the drug concentrations using high-performance liquid chromatography. Pathological examinations were conducted to assess kidney damage. RESULTS: Both drugs lowered the serum uric acid levels. On the other hand, the allopurinol treatment exhibited lower urea and creatinine levels than benzbromarone, indicating potential advantages in reducing kidney damage. Consistent with these findings, the pathological examinations revealed more pronounced kidney damage in the benzbromarone-treated group than in the allopurinol group. PK analysis showed that allopurinol exhibited faster absorption and elimination kinetics than benzbromarone. Both drugs showed a wide distribution in various tissues, with allopurinol and its active metabolite displaying higher excretion levels. CONCLUSIONS AND RELEVANCE: This paper reports the absorption, distribution, metabolism, and excretion processes of allopurinol and benzbromarone in a quail model of HUA. These findings help better understand the PK characteristics of these drugs and promote the use of high uric acid therapy in poultry. In addition, this quail model is a valuable tool for future research on HUA and drug interventions.

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