Correlation between inotropic activity and drug plasma levels of a new cardiotonic agent, MDL 19205

The correlation between the positive inotropic action of a new cardiotonic agent, MDL 19205 (4-ethyl-1,3-dihydro-5-(4-pyridinyl-carbonyl)-2H-imidazol-2-one), and plasma concentrations of the compound after administration to anesthetized dogs was examined. MDL 19205 solution was introduced into either the stomach or the duodenum of the pylorus ligated dog. Duodenal administration (1–10 mg/kg) resulted in dose-related increases in MDL 19205 plasma levels accompanied by substantial, dose-related increases in cardiac contractility, while gastric administration (3–30 mg/kg) produced much lower, highly variable plasma levels of MDL 19205 accompanied by minimal levels of cardiotonic activity. Our results indicate that the cardiotonic activity of MDL 19205 in the anesthetized dog is closely correlated with drug plasma concentrations, and that the duodenum is the preferred site of absorption of MDL 19205, with very little of the drug being absorbed through the stomach. Since the dog has previously been shown to be a good predictor of the kinetics of MDL 19205 in man, our results suggest that the cardiotonic activity and plasma conncentrations of MDL 19205 in man will also be closely linked.