Efficacy and Safety of Flosequinan, Given over 3 Days, Evaluated by Continuous Hemodynamic Monitoring

Abstract

The hemodynamic effects of flosequinan, a new balanced vasodilator, were evaluated in 12 patients with chronic congestive heart failure. The drug was added to diuretics and digitalis and given as an oral dose of 100 mg, once daily in the morning, over 3 days, and hemodynamic monitoring was performed before the first dose and for 72 h thereafter. Hemodynamic improvement, peaking between 1 and 2 h after oral administration, was observed on all 3 days. On day 1 pulmonary capillary wedge pressure (PCWP) was reduced from 27.8 ± 8.6 to 13.0 ± 3.1 mm Hg and cardiac output (CO) increased from 3.3 ± 0.6 to 4.5 ± 0.9 liters/min (p < 0.05). After 12–16 h the effect was slightly attenuated but remained significant at 24 h. A similar response was observed after the doses given on days 2 and3. At 72 h PCWP was 15.5 ± 4.1 mm Hg and CO 3.8 ± 1.1 liters/min (p < 0.05 for the difference from baseline). Heart rate was slightly increased only at 2 h after the dose. Pulmonary arterial and right atrial pressure and systemic and pulmonary vascular resistances were significantly reduced (except for systemic resistance at 72 h). In conclusion, flosequinan produces hemodynamic improvement in patients with chronic congestive heart failure. The response to subsequent doses is similar to the response to the first dose.