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Research Paper Open Access
The influence of ketoconazole on the pharmacokinetics and hypoglycaemic activity of tolbutamide was determined as a preclinical study in normal rabbits with adequate controls. Ketoconazole treatment (20 mg/kg, oral once daily for one week) significantly increased the terminal half-life and AUC 0 --> infinite of tolbutamide (40 mg/kg, oral) when compared to controls. The hypoglycaemic activity of tolbutamide was also enhanced and prologned significantly in ketoconazole treated rabbits. It appears that ketoconazole decreases the in vivo hepatic metabolism of tolbutamide in rabbits.