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

Expert Opinion on Drug Metabolism and Toxicology

Volumn 12, Issue 5, 2016, Pages 567-573

  Packham, David K ^a   Kosiborod, Mikhail ^b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

Author keywords

Hyperkalemia; potassium; renin angiotensin aldosterone system; sodium zirconium cyclosilicate; ZS 9

Indexed keywords

PLACEBO; POTASSIUM; SODIUM ZIRCONIUM CYCLOSILICATE; SILICATE; ZS-9 COMPOUND;

ARTICLE; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; HYPERKALEMIA; HYPOKALEMIA; LONG TERM CARE; MAINTENANCE THERAPY; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POTASSIUM BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); THERMODYNAMICS; ACUTE DISEASE; ANIMAL; CHRONIC DISEASE; DRUG EFFECTS; METABOLISM; PATHOPHYSIOLOGY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; TIME FACTOR;

ACUTE DISEASE; ANIMALS; CHRONIC DISEASE; HUMANS; HYPERKALEMIA; POTASSIUM; RENIN-ANGIOTENSIN SYSTEM; SILICATES; TIME FACTORS;

EID: 84962464661     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2016.1164691     Document Type: Article

References (45)

1. Gumz ML, Rabinowitz L, Wingo CS. An integrated view of potassium homeostasis. N Engl J Med. 2015; 373:60-72.
2. Pani A, Floris M, Rosner MH, Ronco C. Hyperkalemia in hemodialysis patients. Semin Dial. 2014; 27:571-576.
3. Khanagavi J, Gupta T, Aronow WS, et al. Hyperkalemia among hospitalized patients and association between duration of hyperkalemia and outcomes. Ams. 2014; 10:251-257.
4. An JN, Lee JP, Jeon HJ, et al. Severe hyperkalemia requiring hospitalization: predictors of mortality. Crit Care. 2012; 16:R225.
5. Ahn SY, Ryu J, Baek SH, et al. Incident chronic kidney disease and newly developed complications related to renal dysfunction in an elderly population during 5 years: a community-based elderly population cohort study. PLoS One. 2013; 8:e84467.
6. Ahee P, Crowe AV. The management of hyperkalaemia in the emergency department. J Accid Emerg Med. 2000; 17:188-191.
7. Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis and management of hyperkalemia. Pediatr Nephrol. 2011; 26:377-384.
8. Fry A, Farrington K. Management of acute renal failure. Postgr Med J. 2006; 82:106-116.
9. Blumberg A, Weidman P, Shaw S, et al. Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure. Am J Med. 1988; 85:507-512.
10. Weisberg L. Management of severe hyperkalemia. Crit Care Med. 2008; 36:3246-3251.
11. Allon M. Treatment and prevention of hyperkalemia in end-stage renal disease. Kidney Int. 1993; 43:1197-1209.
12. Harel Z, Harel S, Shah PS, et al. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med. 2013; 126:264.e9-24.
13. Batterink J, Lin J, Au-Yeung S, et al. Effectiveness of sodium polystyrene sulfonate for short-term treatment of hyperkalemia. Can J Hosp Pharm. 2015; 68:296-303.
14. Sterns RH, Rojas M, Bernstein P, et al. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol. 2010; 21:733-735.
15. Abramowitz M, Melamed M, Bauer C, et al. Effects of oral sodium bicarbonate in patients with CKD. Clin J Am Soc Nephrol. 2013; 8:714-720.
16. Łoniewski I, Wesson DE. Bicarbonate therapy for prevention of chronic kidney disease progression. Kidney Int. 2014; 85:529-535.
17. Fordjour KN, Walton T, Doran JJ. Management of hyperkalemia in hospitalized patients. Am J Med Sci. 2014; 347:93-100.
18. Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly drugs exacerbate impaired potassium homeostasis. J Gen Intern Med. 1997; 12:646-656.
19. VeltassaTM [package insert]. Redwood City, CA: Relypsa, Inc.; 2015.
20. Aaron KJ, Sanders PW. Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence. Mayo Clin Proc. 2013; 88:987-995.
21. Navaneethan SD, Nigwekar SU, Sehgal AR, et al. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009; 4:542-551.
22. Fonarow GC, Yancy CW, Hernandez AF, et al. Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. Am Hear J. 2011; 161:1024-30.e3.
23. Komajda M, Follath F, Swedberg K, et al. The EuroHeart Failure Survey programme - a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Hear J. 2003; 24:464-474.
24. Cleland JGF, Swedberg K, Follath F, et al. The EuroHeart Failure Survey programme - a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Hear J. 2003; 24:442-463.
25. Albert NM, Yancy CW, Liang L, et al. Use of aldosterone antagonists in heart failure. Jama. 2009; 302:1658-1665.
26. Vardeny O, Claggett B, Anand I, et al. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist. Circulation. 2014; 7:573-579.
27. Palmer BF. A physiologic-based approach to the evaluation of a patient with hyperkalemia. Am J Kidney Dis. 2010; 56:387-393.
28. St Peter WL, Odum LE, Whaley-Connell AT. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease. Pharmacotherapy. 2013; 33:496-514.
29. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the randomized aldactone evaluation study. New Engl J Med. 2004; 351:543-551.
30. Sarafidis PA, Blacklock R, Wood E, et al. Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low-clearance clinic. Clin J Am Soc Nephrol. 2012; 7:1234-1241.
31. Rossignol P, Dobre D, Jj V M, et al. Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from. Circulation. 2014; 7:51-58.
32. Putcha N, Allon M. Management of hyperkalemia in dialysis patients. Semin Dial. 2007; 20:431-439.
33. Pfortmüller CA, Leichtle AB, Fiedler GM, et al. Hyperkalemia in the emergency department: etiology, symptoms and outcome of a life threatening electrolyte disorder. Eur J Int Med. 2013; 24: e59-60.
34. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. New Engl J Med. 2014; 372:222-231.
35. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia. Jama. 2014; 312:2223-2233.
36. Stavros F, Yang A, Leon A, et al. Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One. 2014; 9:e114686.
37. ZS Pharma. Data on file.
38. Fordtran J, Locklear T. Ionic constituents and osmolality of gastric and small-intestinal fluids after eating. Am J Dig Dis. 1966; 11:503-521.
39. Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggest that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015; 88:404-11.
40. Roger SD, Rasmussen HS, Lavin PT, et al. Effect of ZS-9 on serum bicarbonate and BUN in a phase 3 randomized, double-blind, placebo-controlled trial. Am Soc Nephrol. Kidney Week. 2014 Nov 11-16, Philadelphia, Abstract 2743.
41. Singh B, Ash SR, Lavin PT, et al. Acid-base balance in a phase 2 trial of ZS-9 for hyperkalaemia in patients with chronic kidney disease. 51st Eur Ren Assoc Eur Dial Transpl Assoc Congr. 2014 May 31-Jun 3, Amsterdam, Abstract SP251.
42. Stavros F, Singh B, Menoyo J, et al. Assessment of systemic absorption of sodium zirconium cyclosilicate (ZS-9): blood and urine Zr concentration in dogs during a 9-month oral toxicity study. Am Soc Nephrol. Kidney Week. 2015 Nov 3-8, San Diego, Abstract #1586.
43. Kosiborod M, Peacock WF, Packham DK. Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia. New Engl J Med. 2015; 372:1577-1578.
44. US National Institutes of Health. ClinicalTrials.gov. [cited 2015 November 4]. https://clinicaltrials.gov/ct2/show/NCT02163499
45. Winkelmayer WC. Treatment of hyperkalemia from 'Hyper K+ ' Strikeout to Home Run? Jama. 2015; 314:129-130.