Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Abstract

Background and objectives: Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption.

Design, setting, participants, & measurements: We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13-19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study).

Results: In the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (P<0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean±SD) by 1140±316 mg/d, urine magnesium by 45±1 mg/d, and urine sodium by 225±145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P<0.01). Patiromer at 25.2 g/d increased urine calcium by 73±23 mg/d and decreased urine phosphate by 64±40 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing (P=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (P<0.05).

Conclusions: In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate.

Keywords: Animals; Brachyura; Calcium, Dietary; Cations; Cross-Over Studies; Diet; Gastrointestinal Absorption; Intestinal Absorption; Magnesium; Phosphates; Polymers; Potassium; Sodium; calcium; cation exchange; electrolytes; hyperkalemia; patiromer; urinary excretion.

Figure 1.

Study designs. Study design of healthy volunteers treated with patiromer showing controlled diet and urine collection periods in the (A) dose-finding and (B) dose regimen studies. BID, two times per day; BMI, body mass index; Ca, calcium; K, potassium; Mg, magnesium; Na, sodium; P, phosphate; QD, daily; R, date of randomization; TID, three times per day.

Figure 2.

Serum chemistries with patiromer 25.2 g/d during the dose-finding study. Serum chemistries (means±SD) on maximum recommended patiromer dose (25.2 g/d) over time in the dose-finding study. Ca, calcium; K, potassium; Mg, magnesium; P, phosphate.

Figure 3.

Change in urine calcium and phosphate excretion. Mean±SD change in urine calcium (Ca) and phosphate (P) excretion by patiromer dose compared with baseline for both studies (preplanned analyses). Data are from Tables 1 and 3. BID, two times per day; QD, daily; TID, three times per day. *P<0.01 for overall test of patiromer dose differences from analysis of covariance; ^†P=0.01 versus three times per day for pairwise comparison between regimens from t test; ^‡P<0.01 versus three times per day for pairwise comparison between regimens from t test; ^§P=0.02 versus two times per day for pairwise comparison between regimens from t test.

Figure 4.

Twenty-four-hour urine Ca excretion with patiromer 25.2 g/d during the dose-finding study. Twenty-four–hour urine calcium (Ca) excretion (means±SD) by study day for a 25.2-g/d dose of patiromer in the dose-finding study.