Interaction of glimepiride with prokinetic drugs on some of gastrointestinal functions in STZ-induced diabetic mice

Aim: To investigate the effects of metoclopramide, domperidone and erythromycin on blood glucose and serum insulin levels, gastrointestinal motility and carbohydrate absorption in streptozotocin-induced diabetic mice treated with glimepiride. Design and methods: Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit, gastric emptying, xylose and glucose absorption tests. Diabetic groups were treated with glimepiride (10 mg/kg p.o.), metoclopramide (20 mg/kg p.o.), domperidone (20 mg/kg p.o.) or erythromycin (6 mg/kg p.o.) individually or in combination. Results: The test prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg) were effective in decreasing small intestinal transit, enhancing gastric emptying and increasing xylose absorption from the GIT in STZ-induced diabetic mice as compared to diabetic control value. Metoclopramide or erythromycin potentiated the effect of glimepiride (10 mg/kg) on blood glucose level and serum insulin level after repeated dose administration in diabetic mice. Glimepiride (10 mg/kg) significantly decreased small intestinal transit and enhanced gastric emptying in diabetic mice as compared to the diabetic control group. Administration of metoclopramide, domperidone or erythromycin with glimepiride partially antagonized the action of glimepiride on small intestinal transit and gastric emptying in diabetic mice. Administration of metoclopramide, domperidone or erythromycin along with glimepiride significantly increased xylose and glucose absorption as compared to the glimepiride treated group.