Abstract

The purpose of the investigation is to investigate the possible drug interaction between lovastatin (Anti-hyperlipidemic drug) & pioglitazone (Anti-diabetic drug) in both normal & diabetic rats. Generally, increased oxidative stress may contribute to the accelerated atherosclerosis in diabetic patients. However, the effect of statins on glucose metabolism is unclear. Some studies suggested that, statins may cause hyperglycemia by increasing Ca²⁺ concentration in the islet cells leading to decrease in insulin release or by decreasing GLUT 4-mediated peripheral glucose uptake. For years, statins have been used to lower elevated total and LDL cholesterol levels while raising HDL cholesterol levels. Statins act by inhibiting HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A), thus stopping the conversion of HMG-CoA to mevalonate, which is found in the cholesterol synthesis cascade. Unfortunately, several studies have shown increased diagnosis and lack of glycemic control of Diabetic mellitus (DM) when patients were taking high and/or long-term doses of statins, and several mechanisms have been identified that may help explain this side effect. The method used for the estimation of serum glucose levels was GOD/POD method which is simple, reliable, safe and precise. In both the rats the results was found that the pioglitazone has shown hypoglycemic action at the 8^th hr. And after single Oral dose treatment of lovastatin ½ TD, TD and 2 TD followed by single Oral dose administration of pioglitazone, a significant alteration in hypoglycemic activity of pioglitazone was observed when compared with control as it shows initial hyperglycemia followed by hypoglycemic action. After repeated Oral Dose administration of lovastatin ½ TD, TD, 2 TD once daily for 7 days followed by single Oral dose administration of pioglitazone, it was observed that lovastatin exhibited dose dependent significant hyperglycemic action upto 4^th hr and decreases from 6^th hr when compared with control & pioglitazone. And it is concluded that the lovastatin may have the diabetogenic action when administered in combination with pioglitazone and it was clear that there was enhanced hyperglycemic action when given repeatedly. It may be due to the CYP enzyme induction by lovastatin on pioglitazone, it results in the decreased hypoglycemic and anti-diabetic effect of pioglitazone. The dose and frequency of lovastatin must be readjusted when administered with pioglitazone, to avoid excess hyperglycemic effect of lovastatin