PHARMACODYNAMIC AND PHARMACOKINETIC DRUG INTERACTION OF GLIMEPIRIDE AND IRBESARTAN IN ANIMAL MODELS

ABSTRACT

The study was conducted to find out the influence of irbesartan on the pharmacodynamics and pharmacokinetics of glimepiride, which is widely used drug for type II diabetes. Studies were conducted in normal rats; streptozotocin induced diabetic rats and normal rabbits with oral administration of selected doses of glimepiride, irbesartan and their combination. Blood samples were collected from rats/diabetic rats by retro orbital method and marginal ear vein puncture from rabbits at regular intervals of time. All the blood samples were analyzed for glucose by GOD/POD method and serum concentration of glimepiride estimated by HPLC. Glimepiride produced significant hypoglycemia and antihyperglycemia in normal/diabetic rats and in normal rabbits. Therapeutic doses of irbesartan and in combination with glimepiride did not alter the blood glucose levels and the hypoglycemic response in normal rats/ diabetic rats and normal rabbits. There was no significant change in the pharmacokinetic parameters of glimepiride like, AUC, T_1/2, Clearance, Vdss_, Vdarea, MRT, C_max and T_max when given in combination with irbesartan in normal rabbits, the studies indicates there is no pharmacokinetic and pharmacodynamic interaction. The glimepiride is metabolized by CYP 2C9 and irbesartan being metabolized by two CYP isoenzymes primarily CYP2C9 and to minor extent CYP3A4 there was no significant changes in the absorption and elimination of glimepiride by irbesartan was produced in the single dose treatment. Hence the therapy was found to be safe when given  in combination and its use can be encouraged in clinical situation after assessing safety profile in chronic animal studies, healthy volunteers and diabetic patients with hypertension.

Key words: Drug interactions, Glimepiride, Irbesartan, Pharmacodynamics, Pharmacokinetics.