Bushinsky David A, Spiegel David M, Gross Coleman, Benton Wade W, Fogli Jeanene, Hill Gallant Kathleen M, Du Mond Charles, Block Geoffrey A, Weir Matthew R, Pitt Bertram
Division of Nephrology, Department of Medicine, University of Rochester, Rochester, New York.
Relypsa, Redwood City, California.
Clin J Am Soc Nephrol. 2016 Oct 7;11(10):1769-1776. doi: 10.2215/CJN.01170216. Epub 2016 Sep 27.
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).
In the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (<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 <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 (=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (<0.05).
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.
帕替罗姆是一种不被吸收的钾结合聚合物，它以钙作为交换离子。钾结合过程中释放的钙有可能被吸收或结合磷酸盐。由于其结合并非特异性针对钾，帕替罗姆可以结合其他阳离子。在此，我们评估帕替罗姆对健康成年人尿离子排泄的影响，这反映了胃肠道离子吸收情况。
设计、地点、参与者与测量方法：我们在两项研究中分析了帕替罗姆对尿钾、钠、镁、钙和磷酸盐的影响。临床研究单位中接受控制饮食的健康成年人，在剂量探索研究中给予帕替罗姆高达50.4 g/d，分三次服用，共8天；在给药方案研究中，采用交叉设计，给予25.2 g/d，以每日或分服（每日两次或三次）的方式服用18天。基于24小时尿液收集，将基线期（第5 - 11天）的尿离子排泄与治疗期（第13 - 19天；剂量探索研究）的进行比较，并在各方案之间比较每个时期的最后4天（给药方案研究）。
在剂量探索研究中，帕替罗姆使尿钾、尿镁和尿钠呈剂量依赖性降低（每项均<0.01）。25.2 g/d的帕替罗姆使尿钾（均值±标准差）降低1140±316 mg/d，尿镁降低45±1 mg/d，尿钠降低225±145 mg/d。尿钙呈剂量依赖性增加，尿磷酸盐平行降低（均<0.01）。25.2 g/d的帕替罗姆使尿钙增加73±23 mg/d，尿磷酸盐降低64±40 mg/d。尿钾、尿钠和尿镁不受给药方案影响，而与每日三次给药相比，每日一次给药时尿钙的增加显著更低（=0.01）。与每日两次或三次给药相比，每日一次给药时尿磷酸盐的降低也更少（<0.05）。
在健康成年人中，帕替罗姆可降低尿钾、尿钠、尿镁和尿磷酸盐，同时适度增加尿钙。与分服相比，每日一次给予帕替罗姆可使尿钾、尿钠和尿镁得到同等程度的降低，对尿钙和尿磷酸盐的影响较小。
