Description

Volume63,Issue12 Prevention A NOVEL EXTENDED RELEASE FORMULATION OF TORSEMIDE ENHANCES NATRIURESIS WITHOUT LOWERING GFR IN NORMAL HUMAN SUBJECTS. Poster Contributions Hal l C Sunday,March30,2014,9:45a.m.-10:30a.m. Session Title: Prevention: Hypertension I AbstractCategory:21. Prevention: Hypertension Presentation Number: 1184-158 Authors: Wen Shen,Fatima Khwaja, Peter U Feig, MD, Salim Shah, Christo pher Wilcox ,Sarfez Pharmaceuticals ,Inc ,Vienna, VA ,USA ,Georgetown University, Washington, DC Background: Loop diuretics have outstanding acute natriuretic and diuretic actions. However ,their therapeutic efficacy is limited by a modest depletion of body salt or water due to the compensatory increase in renal sodium reabsorption after diuretic effects wear off .We tested the hypothec is that a more prolonged duration of action would enhance salt and water loss. Methods: Ten normal subjects received 20mg of oral torsemide on two occasions while •day-1o f Na+ .They were and optimized to an immediate release (IR) or to an Extended Release (ER) formulation. The ER formulation delivered torsemide in to solution over 12hours. Results: Compared to IR ,the plasma levels of torsemide in the subjects given ER were 59% lower 1-3hours after dosing ,accompanied by a lower naturieses, but were 97% higher 8-10 hours after dosing, leading to a 2-fold increased naturiesis. This resulted in a 2•4-fold prolongation of time to maxim all levels and a >2-fold increase in excreted fluid(1634±385 versus728±445mL;P<0.02) and Na+(98±15versus42±17mmol;P< 0.05)despitean18%reduction in torsemide bio availability. Only after ER was there a reduction on mean blood pressure(-2.9±1.8vs+1.3±1.2 mm Hg;P<0.05)and weight(-0.5±0.2kg;P<0.05)but only after IR was there a significant reduction in creatinine clearance (CCR;-24.5±6.6 ml*min-1per1.73m-2;P<0.005).The higher Na+ excretion and relatively well preserved CCR afterER resulted in a similar increase in fractional excretion of Na+ after ER and IR. Neither drug to a significant loss of potassium. Conclusion: An ER formulation of torsemide led to a doubling of the time to peak plasma levels and loss of salt and water without reducing GFR resulting insignificant reductions in weight and mean BP despite a high salt intake. reference & Trails :- https://www.jacc.org/doi/10.1016/S0735-1097%2814%2961401-7