Vaptans: A Narrative Review of Pharmacokinetics, Pharmacogenetics, and Clinical Applications

Abstract

Vaptans are non-peptide arginine vasopressin (AVP) receptor antagonists essential for modulating water homeostasis. This review evaluates their chemical evolution from peptide analogs to orally bioavailable molecules and summarizes the pharmacokinetic profiles of key agents, including tolvaptan, conivaptan, and mozavaptan. Significant emphasis is placed on the clinical role of tolvaptan as a disease-modifying therapy in autosomal dominant polycystic kidney disease (ADPKD) and its efficacy in syndrome of inappropriate antidiuretic hormone secretion (SIADH). Furthermore, the impact of pharmacogenetic factors, especially CYP3A5 and SVEP1 polymorphisms, is explored as a potential source of inter-individual variability in treatment response. By integrating structural, metabolic, and genetic data, this article highlights the potential for personalized aquaretic therapy and identifies critical safety and monitoring protocols necessary for optimizing clinical outcomes.