RO 13-6438 in congestive heart failure: dose-response relationship after 3 single doses

The dose-response for the new cardiotonic agent RO13-6438 was studied in 6 patients with grade III or IV congestive heart failure. Oral doses of 10, 20, or 30 mg of RO 13-6438 were administered on 3 consecutive days in accordance with a double-blind, randomized cross-over pattern. Hemodynamic changes, which were dose-dependent, included an increase in cardiac index combined with decreases in pulmonary capillary wedge pressure and systemic and pulmonary arterial pressures. Heart rate remained unchanged. The area under the plasma RO 13-6438 concentration time curve and the peak plasma concentration were dose-related. At each measurement, the log concentration of RO 13-6438 correlated with the percent changes in both cardiac index and capillary wedge pressure recorded at that time.