Topical application of the hypoglycemic agent glibenclamide and changes in blood glucose, plasma insulin (IRI) levels and plasma concentration of glibenclamide in normal rats

Abstract

This study was done to determine whether an oral hypoglycemic agent would be absorbed through the skin and consequently lower blood glucose levels. We applied 250 mg or 500 mg of 5% glibenclamide ointment (GO) to the cleanly shaved dorsa (5 × 10 cm) of overnight-fasted male Wistar rats, weighing 250–300 g. Blood samples were collected at 1, 3, 6, 12 and 24 h after the application of GO and blood glucose, plasma insulin (IRI) and the plasma concentration of glibenclamide were determined. The plasma concentration of glibenclamide reached a high level as early as 1 h after application and the level was maintained for 24 h. The plasma concentration of glibenclamide in the 500-mg GO group was higher than in the 250-mg GO group, but even 24 h after application the 250-mg GO group showed a mean value of 206 ng/ml. Mean blood glucose levels in both GO groups at every time point after application were significantly lower than in the control group; with respect to mean IRI levels the opposite was found. Thus, glibenclamide is absorbed through the skin and reaches a level of plasma concentration which induces significant changes in blood glucose and IRI levels. This may well be a new approach to controlling blood glucose levels in patients with diabetes mellitus.