Effects of monensin sodium on digoxin kinetics in conscious male rabbits

ABSTRACT

The investigation was performed on male rabbits equally divided into two groups digoxin treated group and monensin plus digoxin treated group. Digoxin [0.2 mg/kg] was administered orally as a single dose to normal and monensin [6mg/kg for three successive days] pretreated rabbits. Blood samples were obtained at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 12.0 hr. after digoxin administration. Pharmacokinetic parameters of digoxin were indicated by determination of area under the curve from time 0 to time t [AUC[t]], the area under the curve from time zero to infinity[AUC[alpha]], the half-life of the drug [t[1/2]], time required to reach maximum drug concentration[t[max]], maximum drug concentration in the blood [C[max]], drug clearance [C1] and the area under first moment curve [AUMC]. A significant increase in area under the serum concentration -time curve [AUC], increase in maximum concentration [C[max]], and area under moment curve [AUMC] were observed. In addition, Digoxin clearance [C1] was significantly reduced in rabbits pretreated with monensin. While, half-life [t[1/2]] and time required to reach maximum concentration [t[max]] was non significantly changed. The current results suggest that monensin enhance the adverse effects of digoxin in male rabbits. This interaction is played at least in part through an increase of digoxin plasma levels