Research Project
9773469
Project Summary/Abstract Metolazone is a quinazoline sulfonamide with potent thiazide like diuretic activity on the cortical diluting segment, as well as diuretic action on the proximal tubule. Metolazone (orally) is often employed in patients with severe congestive heart failure (CHF) as a supplement to a loop diuretic, as well as in patients with diuretic resistance to loop diuretics. However, metolazone has not been available for IV administration due to its very poor solubility. An IV formulation would be useful in heart failure patients who invariably have poor oral absorption, in patients unable to take oral medications and in patients with loop diuretic resistance when rapid IV administration is difficult to coordinate with peak loop diuretic action. We have developed a new formulation of metolazone for IV administration at a neutral pH, that we believe is not be phlebitic and is effective in diuretic resistant states. Studies proposed in this grant aim to characterize the new formulation and establish its diuretic action in an animal model, initial steps in obtaining an IND to initiate clinical studies.
