ArticleEuropean journal of drug metabolism and pharmacokinetics2025
The Impact of Hyperuricemia on Pharmacokinetics in Sprague-Dawley Rats.
Article in European journal of drug metabolism and pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectiveHyperuricemia (HUA) is a metabolic disease closely associated with hypertension. It can induce liver damage, subsequently affecting drug metabolism. However, its specific impacts and underlying mechanisms remain unclear. Therefore, the pharmacokinetics and cytochrome P450 (CYP450) enzyme activities were investigated.
methodsTwelve healthy Sprague-Dawley rats were randomly assigned into two groups, a control group and an experimental group, with six animals per group. To establish the HUA model, rats in the experimental group received a subcutaneous injection of potassium oxonate (POx) (250 mg/kg), combined with oral administration of a fructose solution (5%, w/v). Serum biochemical parameters were subsequently evaluated, while histopathological examinations of liver and kidney tissues were performed. Plasma amlodipine (ALDP) levels were quantified by employing LC-MS/MS, and pharmacokinetic parameters were analyzed using DAS 3.0 software. Furthermore, activities of six major CYP450 enzyme isoforms were simultaneously determined through the cocktail method.
resultsIn the HUA-induced rats, significant elevations in serum uric acid (SUA), blood urea nitrogen (BUN), and creatinine (Cr) were observed, accompanied by distinct pathological lesions within hepatic and renal tissues. Pharmacokinetic analyses demonstrated marked increases in the peak plasma concentration (C
conclusionThis study successfully established a stable rat model of HUA, and demonstrated that HUA specifically alters drug metabolism by causing liver damage and modulating CYP450 enzyme activities.
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