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An Evaluation of the Pharmacodynamics, Safety, and Tolerability of the Potassium Binder RDX7675
Author(s) -
Pitt Bertram,
Zann Vanessa,
Roe Chris,
Jacobs Jeffrey W.,
Davidson James P.,
Dowd Christine,
Kumaraswamy Padmapriya,
Lin Fangling,
Korner Paul,
Blanks Robert C.,
Rosenbaum David P.
Publication year - 2018
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1102
Subject(s) - medicine , hyperkalemia , pharmacodynamics , excretion , potassium , tolerability , dosing , plasma renin activity , pharmacology , pharmacokinetics , adverse effect , chemistry , renin–angiotensin system , organic chemistry , blood pressure
Hyperkalemia is common in patients with heart failure or chronic kidney disease, particularly those taking renin‐angiotensin‐aldosterone system inhibitors, and can cause arrhythmias and sudden cardiac death. The most widely used treatment, sodium polystyrene sulfonate (SPS), limits gastrointestinal potassium absorption, but has poor palatability. RDX7675 (RDX227675) is the calcium salt of a reengineered polystyrene sulfonate‐based resin with improved palatability over SPS. The pharmacodynamic effects and safety of RDX7675 were assessed in a phase 1, single‐center, randomized, active‐controlled study. Healthy volunteers received nominal active doses of RDX7675 4.6 g twice a day (BID), 4.6 g 3 times a day (TID), 6.9 g BID, 13.7 g daily (QD), 9.2 g TID, or 13.7 g BID (n = 12 each), or equivalent doses of SPS (n = 3 each), for 4 days. RDX7675 dosing increased stool potassium excretion and decreased urinary potassium excretion from baseline. Stool potassium excretion increased by up to 1481 mg/day with RDX7675 (6.9 g BID), and urinary potassium excretion decreased by up to 939 mg/day (13.7 g BID). Similar levels of potassium excretion were observed using QD, BID, or TID dosing of a 13.7 g total daily RDX7675 dose. Few adverse events were reported. In conclusion, repeated oral dosing with RDX7675 over 4 days reduced potassium absorption in healthy volunteers; the results support QD dosing of RDX7675 in future clinical studies.