Pharmacokinetic and Pharmacodynamic Drug Interactions of Eprosartan and Glibenclamide in Healthy Albino Wistar Rats

The study was intended to find out the pharmacokinetic and pharmacodynamic drug interaction of eprosartan, a protype drug used to treat diabetic nephropathy with glibenclamide in healthy Albino Wistar rats following single and multiple dosage treatment. Therapeutic doses (TD) of glibenclamide, TD of eprosartan were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters. In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both eprosartan and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by eprosartan, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it is may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised. In the present study there is a Pharmacokinetic and Pharmacodynamic interaction between eprosartan and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions in pre-clinically are helpful to avoid drug-drug interactions in clinical situation.