Abstract

PHARMACOKINETIC AND PHARMACODYNAMIC DRUG INTERACTIONS BETWEEN THE ANTI HYPERTENSIVE DRUG ENALAPRIL AND THE ANTI DIABETIC DRUG METFORMIN IN NORMAL AND DIABETIC RATS

Anand Arumugam and V. Venkata Rajesham*

ABSTRACT

The aim of the study was to investigate the pharmacokinetic and pharmacodynamic interactions of enalapril and metformin after single and multiple doses in healthy and diabetic albino Wistar rats. Animals were administered therapeutic doses (TD) of enalapril and metformin. Blood glucose levels were measured using the GOD/POD method, plasma concentrations of enalapril and metformin were measured using a sensitive RP-HPLC method, and pharmacokinetic parameters (Cmax, tmax, AUC0-t, AUC0-α, and t1/2) were determined. Mono therapy and combination treatment with metformin and enalapril did not result in significant changes in pharmacokinetic parameters. Co administration with metformin prolonged the half-life of enalapril in diabetic rats. In a single-dose study, the rate of decrease in blood glucose and metformin concentrations was significantly increased in rats treated with both metformin and enalapril compared to rats treated with metformin alone. The mechanism behind this interaction may be due to the inhibition of P-glycoprotein-mediated transport of metformin by enalapril. In this study, a pharmacokinetic and pharmacodynamic interaction between enalapril and metformin was observed.

Keywords: Enalapril, Metformin, Drug interactions, Pharmacokinetics, Pharmacodynamics.