Venkateshwarlu K
Vaagdevi College of Pharmacy, India
Title: Studies on pharmacokinetic interactions and toxicity of metformin with glimepiride
Biography
Biography: Venkateshwarlu K
Abstract
The combination of Metformin and Glimepiride is widely used to treat type 2 diabetes. The present study was carried out to study the pharmacokinetic interactions between these two drugs used in combination. An available RP-HPLC method for simultaneous estimation of Metformin and Glimepiride was revalidated for future use. Albino rats of either sex were randomly distributed into four groups of six animals in each; they are housed in well ventilated Aluminium cages and maintained on uniform diet and temperature with 12hr light and dark cycle. In this study, the blood was collected from orbital sinuses using heparinised capillaries into a micro centrifugation tubes contain anti coagulant at 0, 1, 2, 4, 6, 8, 12 hrs after treatment. Plasma was separated by centrifugation and stored at -20ºC until further analysis. These samples are used to analyze for pharmacokinetic and pharmacodynamic toxicological i.e. SGOT-SGPT, Complete Blood Picture (CBP) and serum Creatinine Clearance. Metformin and Glimepiride levels were estimated by a sensitive RP-HPLC method. This study proves, single and multiple doses Metformin increases plasma concentrations of Glimepiride. There is significant increase in the AUC and decrease in clearance. In single dose studies this change could be because of the transient induction in CYP2C9. When Glimepiride is given in repeated doses (15 days) there could be induction of the microsomal liver CYP2C9 subsequently increasing the metabolism, decreasing clearance of Metformin & increasing the overall AUC. This combination has clearly shown the beneficial effect on the CBP i.e. significant improvement in blood cell count, lymphocytes and neutrophills in particular.