Abstract

STUDY OF PHARMACOKINETIC AND PHARMACODYNAMIC DRUG – DRUG INTERACTION BETWEEN ROSUVASTATIN AND GLIMEPIRIDE IN NORMAL RABBITS

Dr. Nanda Gopal Anitha*, Kalyan Chandra Gurajapu, Tirunagari Mamatha

ABSTRACT

The influence of single and multiple dose effects of the Rosuvastatin on pharmacokinetics and pharmacodynamics were studied in normal rabbits. Five healthy rabbits were selected for each set of experiment. The study was divided into two phases i.e. single and multiple treatment with drugs. Single dose treatment study was divided into three stages. Stage I, three groups of rabbits were administered ½ Therapeutic dose, Therapeutic dose, 2 Therapeutic dose [TD] of glimepiride to obtain the dose effective response of glimepiride. In stage II 1st group of rabbits were treated with rosuvastatin alone and in stage III rabbits were treated with rosuvastatin followed by glimepiride after 30 minutes. In multiple dose treatment study rosuvastatin was given for six days continuously. On seventh day 30 minutes after rosuvastatin treatment glimepiride was administered. The blood samples were withdrawn at different time intervals for estimation of blood glucose levels by GOD- POD method and serum glimepiride levels by RP-HPLC. There was significant rise in pharmacokinetics and pharmacodynamics parameters like Area under curve (AUC), Area under the first movement curve (AUMC) and Peak Concentration (Cmax) of glimepiride with single dose treatment of rosuvastatin. The enhancement of glimepiride response in presence of rosuvastatin may be because of pharmacokinetic mechanism namely inhibition of it’s metabolism coupled with displacement from protein binding site.

Keywords: Hyperlipidimic, Pharmacokinetics, Pharmacodynamics, Drug – Drug interaction, GOD-POD method, RP-HPLC