Modification of the inotropic effect of digoxin by diazepam in rat left atria

There is a pharmacokinetic interaction between digoxin and diazepam that increases the elimination half-life of digoxin. It may be due to a reduction of digoxin tissue concentrations and to an enhanced effect of diazepam on digoxin binding to plasma albumin. Diazepam (10(-5) M) also induces a positive inotropic effect in guinea-pig isolated atria. In a study of a possible pharmacodynamic interaction between both drugs, the inotropic response to digoxin has been examined in rat isolated atria in the presence of diazepam. The atria were kept in Tyrode at 37 degrees C, bubbled with 95% O2 and 5% CO2 and electrically stimulated at twice the threshold voltage. The results indicate that diazepam induces an inotropic effect at 10(-5) M (P less than 0.05) and reduces (P less than 0.05) at 10(-9), 10(-7) and 10(-5) M the inotropic response to digoxin (10(-5) M).