Tolvaptan in Hyponatremia – A Pharmacologic approach

Abstract

Tolvaptan is the first orally active vasopressin receptor 2 antagonist approved by FDA in 2009 for the treatment of clinically significant hypervolemic and euvolemic hyponatremia associated with heart failure, syndrome of inappropriate antidiuretic hormone secretion, liver cirrhosis. Binding of vasopressin to V2 receptors which are located on renal collecting duct cells were competitively inhibited by Tolvaptan thus prevents vasopressin-mediated activation of these receptors and leads to an increase in the water permeability of the collecting duct causing an increase in the concentration of urine, results in an increase in free water clearance, a decrease in urine osmolality and a fall in serum sodium concentration. Tolvaptan is different from other conventional diuretics because it does not stimulate the sodium channel and increases free water excretion without affecting urinary sodium and potassium excretion. It is metabolized principally via the cytochrome P 450 (CYP 3A) isoenzymes and is eliminated by routes other than renal. Concurrent administration of tolvaptan with ketoconazole or other strong CYP 3A inhibitor decrease the total clearance of tolvaptan and increases tolvaptan concentrations. Urine sodium potassium ratio, weight loss, soluble CD14, urinary aquaporin 2 levels are known predictors of tolvaptan response. Tolvaptan is associated with decreased cost and high effectiveness.