title: Pharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Here we discuss mechanisms of potassium homeostasis and preclinical and clinical studies that present pharmacokinetics/pharmacodynamics, efficacy and safety profiles of ZS-9.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Melbourne Renal Research Group and Departments of Medicine , University of Melbourne and Nephrology, Royal Melbourne Hospital , Melbourne , VIC , Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: Packham
authors.affiliation: b Saint Luke's Mid America Heart Institute , University of Missouri , Kansas City , MO , USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kosiborod
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D006947:Hyperkalemia / Q000188:drug therapy* / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D017640:Silicates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D017640:Silicates; C000597310:sodium zirconium cyclosilicate; D011188:Potassium
keywords: Hyperkalemia; ZS-9; potassium; renin-angiotensin-aldosterone system; sodium zirconium cyclosilicate