Effect of allopurinol on tolbutamide pharmacokinatics and hypoglycaemic activity in rabbits

ABSTRACT

The effect of allopurinol on pharmacokinetic parameters and hypoglycemic activity of tolbutamide was assessed in fasted rabbits. Pretreatment of animals with allopurinol [30 mg/kg orally] 2 hours before tolbutamide injection [50 mg/kg i.v.] resulted in a significant increase in plasma tolbutamide levels compared to those of rabbits received tolbutamide alone. The plasma half life [t1/2] of tolbutamide increased from 6.60 to 12.83 hours by allopurinol pretreatment. The hypoglycemic activity of tolbutamide was also significantly enhanced in rabbits received allopurinol. These results suggested the importance of tolbutamide dosage adjustment when allopurinol is given concurrently