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

Studies were conducted in normal rats, alloxan induced diabetic rats and normal rabbits with oral administration of selected doses of gliclazide, olanzapine and their combination with adequate wash out periods in between treatments. Blood samples were collected from rats and rabbits at regular intervals of time and were analysed for glucose by GOD/POD method and for gliclazide by HPLC method. Glicazide produced hypoglycemia and antihyperglycemia in normal/diabetic rats with peak activity at 1h & 8h and 3h & 10 h respectively and in rabbits at 2 h. Therapeutic dose of olanzapine alone did not alter the normal blood glucose level and it did not alter the hypoglycemic response produced by gliclazide in combination. The same phenomenon observed in diabetic rats and rabbits also. There was no significant change in the serum levels and pharmacokinetic parameters of gliclazide when given in combination with olanzapine in normal rabbits. Hence it is concluded that single dose treatment with olanzapine has no influence on pharmacodynamics/ pharmacokinetics of gliclazide. Since the combination was found to be safe in two dissimilar species, the combination might be safe in humans also.