Urodilatin
A kidney-derived 32-amino-acid natriuretic peptide; synthetic ularitide was tested by infusion in acute heart-failure trials.
Overview
Urodilatin is a 32-amino-acid natriuretic peptide first isolated from human urine; it is structurally identical to atrial natriuretic peptide (ANP) with a four-amino-acid N-terminal extension. It is produced in the kidney and is studied for natriuretic, diuretic, and vasodilatory actions. Synthetic urodilatin (ularitide) has been evaluated in clinical trials for acute heart failure.
Mechanism
Urodilatin activates the natriuretic peptide receptor NPR-A (GC-A), raising intracellular cGMP. This drives sodium and water excretion, relaxes vascular smooth muscle, and reduces cardiac preload and afterload. The N-terminal extension distinguishes it from ANP and is proposed to alter its renal handling and degradation profile.
Dosing
Clinical studies of ularitide in acute heart failure used continuous intravenous infusion in hospitalized patients. Research applications are protocol-specific, and no approved indication exists.
- Intravenous infusion is the route used in clinical heart-failure studies
- Renal and hemodynamic effects are dose-dependent
- All use is investigational
Expected Effects
- Increased sodium and water excretion in healthy and heart-failure settings
- Reduced filling pressures and improved hemodynamics in acute heart-failure studies
- Clinical-outcome endpoints in the large phase 3 program were neutral
Side Effects & Tolerability
Hypotension is the main dose-limiting effect observed with infusion. In the large phase 3 heart-failure program, ularitide did not improve the primary clinical endpoint, which frames its current status as investigational.
Storage
Lyophilized peptide should be stored cold and desiccated, protected from light and moisture. Reconstituted solutions are typically aliquoted and refrigerated or frozen, avoiding repeated freeze-thaw cycles.