The effect of evocalcet on vagus nerve activity of the gastrointestinal tract in miniature pigs.

Shin Tokunaga,Takehisa Kawata,Olivier Barbier

doi:10.1371/journal.pone.0245785

Abstract

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.

Highlights

Secondary hyperparathyroidism (SHPT), characterized by elevated serum parathyroid hormone (PTH) levels, is a common mineral bone disorder in patients with chronic kidney disease (CKD) [1]
To evaluate the effects on serum PTH and calcium levels, miniature pigs were orally treated with cinacalcet or evocalcet
Cinacalcet effectively suppresses the PTH and calcium levels in patients with SHPT, it frequently induces GI events, which often results in poor adherence

Summary

Introduction

Secondary hyperparathyroidism (SHPT), characterized by elevated serum parathyroid hormone (PTH) levels, is a common mineral bone disorder in patients with chronic kidney disease (CKD) [1]. High serum PTH levels often cause abnormal mineral metabolism that is associated with risks of vascular calcification, fracture, and cardiovascular (CV) mortality [2]. Numerous clinical reports have assessed the efficacy of cinacalcet on the treatment of SHPT [4,5,6,7]. In these reports, cinacalcet contributed to the adequate control of serum PTH and Ca levels and to reductions in the number of parathyroidectomies (PTx), CV events, fractures, hospitalizations, and mortality in patients with SHPT. It was reported that cinacalcet may be associated with nausea in 32% of patients and with vomiting in 30% of patients in a total of 371 patients [9]. GI intolerability often limits the dose of cinacalcet and causes poor compliance or discontinuation

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Conclusion