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Renal insufficiency is a factor which predisposes to hypoglycemic accidents in subjects treated with hypoglycemic sulfonylureas. Glibenclamide (glyburide) is eliminated from the body mainly by metabolism, with the result that renal insufficiency has little effect on its biotransformation. In order to determine to what extent the retention of the metabolities intervenes in such hypoglycemic accidents, rats with ligatured ureters received intraperitoneal injections of 1 mg/kg glibenclamide or hydroxy-glibenclamide (the main metabolite), or of saline. For each animal there was a control animal which had undergone a simulated operation. For six rats with renal insufficiency, glibenclamide caused hypoglycemia of the same intensity as in the control group but more prolonged. With hydroxy-glibenclamide the glycemia was signficantly lower than in the control group. Hydroxy-glibenclamide has an obvious hypoglycemic activity which represents 1/6 of that of the parent drug, but 50--100 times that of tolbutamide. Its retention contributed to the intensification and prolongation of the hypoglycemic effect of glibenclamide in rats with renal insufficiency.
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