The effects of tolbutamide and glibenclamide on intestinal glucose absorption

At low mucosal concentrations the hypoglycaemic sulphonylureas, tolbutamide and glibenclamide, reduced active glucose transfer by sacs of everted rat jejunum. At high drug concentrations glucose metabolism was reduced to levels observed under anaerobic conditions. It is possible that the sulphonylureas disrupt intracellular supplies of ATP, thereby affecting the intestinal transport mechanism. Long-term oral administration of glibenclamide to rats had no effect on weight gain, blood sugar levels or transfer, uptake and metabolism of glucose by gut sacs in vitro . Incubation of an open-ended gut loop, allowing replacement of both mucosal and serosal fluids, demonstrated that response to drug exposure was slow and that recovery from exposure even to high concentrations possible. It therefore seems likely than an oral dose in man under normal conditions would not maintain a sufficiently high intraluminal concentration long enough for a significant change in glucose absorption. Even if some imbalance did occur, removal of the inhibitory influence would allow a return to normal conditions.