Abstract 12397: Chronic Diuretics Treatment in Dogs: Novel Diuretic ROMK Inhibitor versus Furosemide

Long-term use of loop diuretics (LD) in congestive heart failure (CHF) frequently leads to a state of reduced responsiveness, often refered to as a diuretic-resistant (DR) state. Furosemide is a LD with several shortcomings: it is short acting, it displays high pharmacokinetic variability, and it requires intact luminal transport for effective target engagement. We have developed an inhibitor of the Renal Outer-Medullary K+ channel (ROMKi) that has several potential advantages over existing LDs for the treatment of volume overloaded states: it has a longer half-life, it can access its target from both the plasma and urine compartments, and should function to inhibit sodium reabsorption in both the thick ascending loop of Henle and in the distal collecting duct. This study describes the results of chronic treatment of equinatriuretic doses of furosemide versus ROMKi in a dog study. Male beagles were administered furosemide, ROMKi or an inert vehicle for 4 months. Body weight loss (BWL) due to extracellular...