R&D Division, Nephrology Research Laboratories, Nephrology R&D Unit, Kyowa Kirin Co., Ltd., Shizuoka, Japan.
PLoS One. 2021 Jan 22;16(1):e0245785. doi: 10.1371/journal.pone.0245785. eCollection 2021.
Evocalcet is a novel calcimimetic agent with fewer gastrointestinal (GI) adverse effects compared to cinacalcet. Although it is thought that cinacalcet induces GI side effects through the direct stimulation of the calcium receptor (CaR) expressed in the GI tract, the differences in the direct stimulatory effects of these two drugs on the GI tract have not been reported. In this study, we analyzed the difference in the GI effects of these two calcimimetic agents using miniature pigs by detecting vagus nerve stimulation after oral administration of the agents. Although cinacalcet induced vomiting in miniature pigs, evocalcet never induced emetic symptoms. A significant increase in the vagus nerve action potentials was observed after the administration of cinacalcet. Although the increase of that after the administration of evocalcet was mild and not significant in comparison to that in the vehicle group, it was not significantly different from the vagus nerve action potentials after cinacalcet treatment.
依卡路特是一种新型的拟钙剂,与西那卡塞相比,胃肠道(GI)不良反应较少。虽然人们认为西那卡塞通过刺激胃肠道中表达的钙受体(CaR)直接引起胃肠道副作用,但这两种药物对胃肠道的直接刺激作用的差异尚未报道。在这项研究中,我们通过检测口服给药后迷走神经刺激,使用小型猪分析了这两种拟钙剂的胃肠道作用差异。虽然西那卡塞引起小型猪呕吐,但依卡路特从未引起呕吐症状。西那卡塞给药后迷走神经动作电位显著增加。虽然依卡路特给药后的增加幅度与对照组相比较轻且不显著,但与西那卡塞治疗后的迷走神经动作电位无显著差异。