EFFECT OF OLMESARTAN ON PHARMACODYNAMICS AND PHARMACOKINETICS OF GLIMEPIRIDE AND METFORMIN COMBINATION IN ANIMAL MODELS

To establish the safety and efficacy of drug-drug combinations in diabetic hypertensive patients, the present study was designed to identify the pharmacodynamic and pharmacokinetic influence of olmesartan on glimepiride + metformin combination in normal rats, diabetic rats and normal rabbits using treatment of single and multiple doses. Blood samples were analyzed for blood glucose by GOD/POD method, insulin by elISA and serum glimepiride levels by HPlC method at pre-determined time intervals. Olmesartan showed significant synergistic hypoglycemic activity with glimepiride + metformin as well as elevated serum insulin levels in single and multiple-dose combinations in both rats and rabbits. The pharmacokinetic interactions of this combination are evidenced by a significant increase in AUMC0-t, AUMC0-∞ and MRT and there is a decrease in clearance (Cl) of glimepiride + metformin with single and multiple-dose treatment of olmesartan. Hence, care must be taken by physicians while prescribing olmesartan and glimepiride + metformin combination in a clinical situation.