Pharmacodynamic and Pharmacokinetic Drug Interaction Of Gliclazide and Olanzapine in Animal Models

The study was conducted to find out the influence of risperidone on the pharmacodynamics and pharmacokinetics of gliclazide, which is widely used drug for type II diabetes. Studies were conducted in normal rats; alloxan induced diabetic rats and normal rabbits with oral administration of selected doses of gliclazide, risperidone and their combination with adequate wash out periods in between treatments. Blood samples were collected from rats/rabbits by retro orbital/marginal ear vein puncture respectively at regular intervals of time. All the blood samples were analyzed for glucose by GOD/POD method and for gliclazide by HPLC. Gliclazide produced significant hypoglycemia and antihyperglycemia response in normal/diabetic rats and in rabbits. Therapeutic dose of risperidone alone did not alter the normal blood glucose level and the hypoglycemic response produced by gliclazide in combination in normal rats. Similar phenomenon was observed both in diabetic and normal rabbits. There was a significant change in the pharmacokinetic parameters of gliclazide like, AUMC, t 1/2 , K e, V dss clearance and MRT when given in combination with risperidone in normal rabbits, indicating the change in elimination pattern of gliclazide in the presence of risperidone . This might be due to the increase in the pH of urine by risperidone which might be facilitated the elimination of gliclazide, a weakly acidic drug in later hours. The single dose treatment did not produce the change in the hypoglycemic activity, but multiple dose treatment may reduce the gliclazide activity. Hence the therapy with the combination needs adjustment of dosing intervals between the treatments.