Någård Mats, Singh Bhupinder, Boulton David W
Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Department of Medicine, University of California, Irvine, CA, USA.
Clin Kidney J. 2020 Dec 13;14(8):1924-1931. doi: 10.1093/ckj/sfaa237. eCollection 2021 Aug.
Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a potassium (K) binder for treatment of hyperkalemia in adults. SZC binds K in exchange for sodium (Na) or hydrogen (H) in the gastrointestinal tract, conveying potential for systemic absorption of Na.
This single-center Phase 1 study evaluated the effects of SZC on Na and K excretion in healthy, normokalemic adults. During an initial run-in period (Days 1-2), participants started a high K/low Na diet. After baseline (Days 3-4), SCZ 5 or 10 g once daily (QD) was administered (Days 5-8). The primary endpoint was mean change in urinary Na excretion from baseline (Days 3-4) to the treatment period (Days 7-8).
Of 32 enrolled participants, 30 entered and completed the study; the first 15 received 5 g and the next 15 received 10 g. Nonsignificant changes from baseline in urinary Na excretion were observed with SZC 5 g (mean ± SD -0.93 ± 25.85 mmol/24 h) and 10 g (-5.47 ± 13.90 mmol/24 h). Statistically significant decreases from baseline in urinary K excretion (mean ± SD -21.17 ± 21.26 mmol/24 h; P=0.0017) and serum K concentration (-0.25 ± 0.24 mmol/L; P=0.0014) were observed with the 10-g dose. There were few adverse events and no clinically meaningful changes in vital signs or laboratory safety measures.
Treatment with SZC 5 or 10 g QD reduced serum K concentration and urinary K excretion, with no significant effect on urinary Na excretion, and was well tolerated.
环硅酸锆钠（SZC；原称ZS-9）是一种用于治疗成人高钾血症的钾（K）结合剂。SZC在胃肠道中结合钾以交换钠（Na）或氢（H），存在钠全身吸收的可能性。
这项单中心1期研究评估了SZC对健康、血钾正常的成年人钠和钾排泄的影响。在初始导入期（第1 - 2天），参与者开始高钾/低钠饮食。在基线期（第3 - 4天）后，每天一次给予5或10克SZC（第5 - 8天）。主要终点是从基线期（第3 - 4天）到治疗期（第7 - 8天）尿钠排泄的平均变化。
32名入组参与者中，30名进入并完成了研究；前15名接受5克，后15名接受10克。5克SZC组（均值±标准差 -0.93±25.85毫摩尔/24小时）和10克SZC组（-5.47±13.90毫摩尔/24小时）尿钠排泄与基线相比无显著变化。10克剂量组尿钾排泄（均值±标准差 -21.17±21.26毫摩尔/24小时；P = 0.0017）和血清钾浓度（-0.25±0.24毫摩尔/升；P = 0.0014）与基线相比有统计学意义的下降。不良事件较少，生命体征或实验室安全指标无临床意义的变化。
每天一次给予5或10克SZC治疗可降低血清钾浓度和尿钾排泄，对尿钠排泄无显著影响，且耐受性良好。
