title: Mechanism of Action and Pharmacology of Patiromer, a Nonabsorbed Cross-Linked Polymer That Lowers Serum Potassium Concentration in Patients With Hyperkalemia.
abstract: Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin-angiotensin-aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin-angiotensin-aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance.
authors: Relypsa, Inc, Redwood City, CA, USA lli@relypsa.com.
authors: Lingyun
authors: L
authors: Li
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Stephen D
authors: SD
authors: Harrison
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: M Jamie
authors: MJ
authors: Cope
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Craig
authors: C
authors: Park
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Lawrence
authors: L
authors: Lee
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Faleh
authors: F
authors: Salaymeh
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Deidre
authors: D
authors: Madsen
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Wade W
authors: WW
authors: Benton
authors: Relypsa, Inc, Redwood City, CA, USA.
authors: Lance
authors: L
authors: Berman
authors: Tricida, Inc, South San Francisco, CA, USA Guest Editor: Sharon L. Hale.
authors: Jerry
authors: J
authors: Buysse
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002614:Chelating Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D066237:Intestinal Elimination; D011108:Polymers / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D011108:Polymers; C568789:patiromer; D011188:Potassium
keywords: RAASi; chronic kidney disease; hyperkalemia; patiromer; potassium