Pharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia

Introduction: Hyperkalemia is a common electrolyte disorder that arises from dysfunctional homeostatic mechanisms or as a consequence of decreased renal function. Sodium zirconium cyclosilicate (ZS-9) is a potential new therapy for hyperkalemia in both acute and chronic settings.Areas Covered: Here we discuss mechanisms of potassium homeostasis and preclinical and clinical studies that present pharmacokinetics/pharmacodynamics, efficacy and safety profiles of ZS-9.Expert Opinion: ZS-9 has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium. The potassium lowering action of ZS-9 is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration by irreversibly eliminating excess potassium rather than acting via intracellular translocation. Its safety profile, including gastrointestinal events, has been generally similar to that of placebo, with the exception of infrequent but manageable events of peripheral edema and transient hypokalemia. ZS-9 has demonstrated potential for enabling renin-angiotensin-aldosterone system inhibitors in mid-term studies, with long-term studies ongoing.