Dose fixing is the major troublesome parameter to elucidate for most of the oral antidiabetic agents even after preclinical toxicity studies. So our aim is to fix the dose that could be of maximum therapeutic efficacy with safer therapeutic margin of the drug used by means of incremental dose response study and area under the curve. Sprague dawley rats were made diabetic with Streptozotocin (45mg/kg/i.p.,). After 16 hours fasted condition the animals were subjected to OGTT with 1g/kg/p.o., of glucose before commencement of the treatment. Starting from the 30th min of glucose loading, the Sedimental Extract of Tinospora cordifolia (SETc) at incremental doses, from the minimum of 250mg/kg/p.o., to the maximum of 1000 mg/kg/p.o., (maximum dose selected from chronic toxicity studies) were administered to the respective groups and the AUC of the blood glucose concentration and the effective dose of the test drug were studied. The onset of action of all the doses of the SETc originates from the 60th min of the drug administration and showed the biological responses in a concentration dependant manner. The blood glucose concentration of the treated rats found to be inversely proportional to the concentration gradient. SETc at 1000 mg/kg showed its maximal dose response effect and marginal therapeutic regimen for its antidiabetic activity with lesser risk of hypoglycemic shock. From the IDF, AUC and EDF data’s obtained, it was evidenced that the application of this modified method as a valuable tool for finding safer marginal dose for some other antidiabetic agents also.
Loading....