Abstract

EFFECT OF LINEZOLID ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF METFORMIN IN NORMAL AND DIABETIC RATS

Keerthana Arra*, Bheemreddy Thrinitha, Shiva Shanmukhi Mukkala and Bhargav Bhongiri

ABSTRACT

Drug interactions are an increasingly important cause of adverse drug reactions. This was recognized over 100years ago. All effective drugs have the potential for producing both benefits and risks associated with desired and undesired effects. The present study was conducted to evaluate the effect of linezolid on the pharmacokinetics and pharmacodynamics of metformin in normal and alloxan induced diabetic rats. The specific aims of present study are. To Validate the RP-HPLC method for analysis of Metformin from in-vitro and in-vivo plasma samples. To perform single dose and multiple dose studies in normal and diabetic rats for evaluation of Pharmacokinetic and Pharmacodynamic parameters. Estimation of blood glucose levels by GOD-POD method. To investigate the influence of Linezolid on the pharmacokinetics and pharmacodynamics of Metformin. To find out the pharmacokinetic parameters of Metformin and its interaction mechanism this helps to avoid adverse effects without compromising therapeutic benefit. Experiments were performed with wistar rats procured from Mahaveera Enterprises (Hyderabad, A.P., India), weighing between 180 to 210gms. The animals were housed in colony cages (four per cage) under conditions of standard lighting, temperature (22±1oc) and humidity for at least one week before the beginning of experiment, to adjust to the new environment and to overcome stress possibly occurred during transit. During this period, they had free access to food and water. In multiple dose studies Linezolid increased the antidiabetic activity of Metformin by increasing the bioavailability of Metformin and these results were found to be statistically significant. Well-designed controlled studies in human beings are needed to confirm the interaction. So, the initial investigations reveal that combination of Metformin and Linezolid should be used with caution in a clinical situation, especially in patients with diabetic foot ulcers.

Keywords: RP-HPLC, GOD-POD, Metformin, Well-designed.