Study on Drug-Drug Interaction between Carvedilol and Gliclazide in Normal and Diabetic Rats

The aim of this work was to study the drug-drug interaction between carvedilol, a non selective beta-blocker, with gliclazide (sulfonyl urea derivative used in type-II diabetes). Multidrug therapy is required in conditions of diabetes and hypertension present in the same individual. During this time there is every possibility of drug-drug interaction. It was reported that when beta-blockers and sulfonylurea derivatives are administered concomitantly beta-blockers will enhance hypoglycemic activity of oral antidiabetic drugs and cause hypoglycemic complication. Considering this drug-drug interaction the present work was planned to verify the above reported drug-drug interaction with combination of different doses of carvedilol (5, 10, and 20 mg/Kg) and single dose of gliclazide (10 mg/Kg), and combination of repeated doses of carvedilol followed by a single dose of gliclazide in both normal healthy and streptozotocin induced diabetic rats. 0.1 N NaOH is used as vehicle for both carvedilol and gliclazide. Streptozotocin was used to induce diabetes in rats and serum glucose levels were analysed by using GOD/POD method on semi-autoanalyzer (ERBA Mannheim, HEM-5 plus v2), at prefixed time intervals like 0, 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Gliclazide 10 mg/Kg has exhibited a significant hypoglycemic activity and antidiabetic activity in normal and streptozotocin induced diabetic rats. Carvedilol at different doses as mentioned above also produced a significant and dose dependent hypoglycemic and antidiabetic activity in normal/streptozotocin induced diabetic animals. Carvedilol in combination with single dose of gliclazide and also repeated doses followed by single dose of gliclazide combination produced a significant reduction in hypoglycemic and antidiabetic activity of gliclazide. From the experimental study it was noted that dose of gliclazide has to be readjusted during these drugs combination. However an opposite effect is noted than the theoretical effect reported in literature i.e., beta-blocker carvedilol reduced the antidiabetic activity of gliclazide rather than potentiation. So the interaction has to be checked in human volunteers with hypertension and diabetic conditions.