AVP receptor antagonists as aquaretics: Review and assessment of clinical data

ABSTRACT

The antidiuretic hormone arginine vasopressin (AVP) is primarily responsible for regulating osmotic and volume homeostasis of body fluids, largely through binding to vasopressin type 1A (V_1A) and type 2 (V₂) receptors. Increased AVP secretion leads to decreased free water excretion with resulting water retention, and can cause dilutional hyponatremia. A new class of medications known as AVP receptor antagonists induces free water diuresis without natriuresis or kaliuresis, an effect termed aquaresis. Numerous clinical trials show AVP antagonists to be effective at increasing free water excretion and serum sodium in patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion or edema-forming states such as congestive heart failure and cirrhosis. This article reviews clinical trial data on the AVP antagonists in late development (lixivaptan, satavaptan, and tolvaptan) and recently approved for marketing (conivaptan).