The metabolic transformation of phenylbutazone in the alloxan diabetic rat

1. In vivo and in vitro rates of metabolism of phenylbutazone have been studied in normal, alloxan diabetic and insulin-treated diabetic rats. 2. In the in vivo experiments urine was collected periodically after an oral dose of the drug and analysed spectrophotometrically for unchanged phenylbutazone and its metabolites. Concurrently, blood specimens were also obtained and similarly analysed. The results revealed a slower metabolic rate of the drug in the diabetic animals than in the controls, which was commensurate with the severity of the diabetic state. 3. The pattern of the metabolic rate of phenylbutazone incubated with microsomal preparations was essentially similar to that observed in the intact animal. 4. Insulin treatment brought back the metabolic rate to near normal levels. 5. It is suggested that the anomolies in the metabolism of phenylbutazone observed in the alloxan diabetic rat could be ascribed, in the main, to a deficiency in NADPH and/or in microsomal and certain other hepatic enzymes.