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.

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

“…Ca rather than sodium (Na) was chosen to prevent additional Na administration and the potential for Na absorption and volume overload when treating patients who are hyperkalemic, many of whom have heart failure or CKD (2,3). K binding by patiromer may occur in proximal segments of the gastrointestinal (GI) tract but is greatest in the colon, where active K secretion results in high luminal K concentrations, the pH is optimal for ion exchange, and the polymer has the longest residence time (1,(4)(5)(6). Patiromer encounters a series of different cation environments as it traverses the GI tract (1,7).…”

“…K binding by patiromer may occur in proximal segments of the gastrointestinal (GI) tract but is greatest in the colon, where active K secretion results in high luminal K concentrations, the pH is optimal for ion exchange, and the polymer has the longest residence time (1,(4)(5)(6). Patiromer encounters a series of different cation environments as it traverses the GI tract (1,7). Its cation-binding properties suggest that it has the potential to bind other cations, including Na and magnesium (Mg) (1,7,8).…”

“…Patiromer encounters a series of different cation environments as it traverses the GI tract (1,7). Its cation-binding properties suggest that it has the potential to bind other cations, including Na and magnesium (Mg) (1,7,8). This potential binding is dependent on the ambient pH as well as the ion concentration along the GI tract (1,5).…”

“…Patiromer is a nonabsorbed potassium (K) binder that uses calcium (Ca) as the counterion for K exchange (1). Ca rather than sodium (Na) was chosen to prevent additional Na administration and the potential for Na absorption and volume overload when treating patients who are hyperkalemic, many of whom have heart failure or CKD (2,3).…”

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

“…It is approved for the treatment of hyperkalaemia in the USA and in Europe 10, 11, 12. Patiromer has been shown to reduce serum K + in hyperkalaemic patients with CKD with or without other co‐morbidities, such as HF, diabetes mellitus, and/or hypertension 13, 14, 15.…”