Influence of dietary protein on the disposition and metabolism of phenylbutazone in rats

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Abstract
Influence of dietary protein on the disposition and metabolism of phenylbutazone was investigated in male rats fed ad libitum a 21% (control) or a 5% (low) protein diet for 3 weeks. Phenylbutazone and its metabolites were assayed by high-pressure liquid chromatography. Dietary protein deficiency was associated with a decrease in the conversion of phenylbutazone into oxyphenbutazone by 9000 × g liver supernatant of protein-deficient rats. Also, dietary protein deficiency was associated with a decrease in the urinary excretion of various metabolites of phenylbutazone, namely, oxyphenbutazone γ-hydroxyphenylbutazone, β-hydroxyphenylbutazone, p,γ-dihydroxyphenylbutazone, and an unknown metabolite (not identified). Pretreatment with phenobarbitone or phenylbutazone led to an increase in the hepatic metabolism of phenylbutazone and the urinary excretion of various metabolites in both groups of animals. Within 5 min after an injection of phenylbutazone, plasma contained oxyphenbutazone; the area under the curve of oxyphenbutazone was significantly greater in protein-deficient rats than in controls possibly due to a greater accumulation. It is concluded that dietary protein deficiency is associated with a decrease in the disposition and metabolism of phenylbutazone in rats.

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