Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine , Isehara, Japan.
R&D Division, Kyowa Kirin Co., Ltd , Tokyo, Japan.
Expert Rev Endocrinol Metab. 2020 Sep;15(5):299-310. doi: 10.1080/17446651.2020.1780911. Epub 2020 Jun 18.
The calcium-sensing receptor is an important treatment target for secondary hyperparathyroidism (SHPT) in patients undergoing dialysis. In addition to vitamin D receptor activator, cinacalcet has recently been widely used for SHPT management, and the significant suppression of parathyroid hormone (PTH) with better control of serum calcium and phosphorus has been reported. However, low adherence and insufficient dose escalation mainly due to frequent gastrointestinal adverse events, still remain as major issues. To overcome these unmet needs, we have developed a new oral calcimimetic agent evocalcet, which has recently been approved by the Pharmaceutical Affairs Act in Japan.
PubMed was searched from inception until April 2020 with the word evocalcet to summarize the development of this new calcimimetic agent, its pharmacokinetics, and the results of clinical trials, along with an overview of the differences among calcimimetic agents. This review also includes the management of SHPT with a focus on calcimimetics.
Evocalcet evoked fewer gastrointestinal-related adverse events while suppressing PTH at a lower dose than cinacalcet. These data suggest evocalcet may contribute to better adherence and sufficient dose escalation in patients with SHPT. Whether or not evocalcet improves clinical outcomes remains to be elucidated.
钙敏感受体是透析患者继发性甲状旁腺功能亢进症(SHPT)的重要治疗靶点。除了维生素 D 受体激动剂,西那卡塞最近也被广泛用于治疗 SHPT,其能够显著抑制甲状旁腺激素(PTH),更好地控制血清钙和磷。然而,由于胃肠道不良反应频繁,药物的依从性差且剂量增加不足仍然是主要问题。为了克服这些未满足的需求,我们开发了一种新的口服拟钙剂依卡路特,最近已被日本《药品法》批准。
通过在 PubMed 中搜索关键词 evocalcet,检索从创建到 2020 年 4 月的相关文献,以总结这种新型拟钙剂的开发、药代动力学以及临床试验结果,并概述不同拟钙剂之间的差异。本文还重点介绍了甲状旁腺功能亢进症的治疗,包括拟钙剂的应用。
与西那卡塞相比,依卡路特在降低 PTH 水平的同时,引发的胃肠道相关不良反应更少。这些数据表明,依卡路特可能有助于提高 SHPT 患者的药物依从性和充分的剂量调整。依卡路特是否能改善临床结局仍有待阐明。