Cinacallcet modifies the pH of solutions in vitro: possible implications for gastro-intestinall side effects in vivo

Sir, The US-based Federal Drug Agency (FDA) and the European Medicines Agency have approved the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in patients on dialysis, and in those with parathyroid carcinoma [1]. Cinacalcet is effective and, overall, well tolerated [2]. However, in clinical trials, it has been observed that certain patients on cinacalcet have episodes of hypocalcaemia (1.4% of patients), nausea (∼31%) and vomiting (∼27%), much more than in patients receiving a placebo [3,4]. Gastrointestinal intolerance, with vomiting in particular, has been found to be dose-related, and is the most common reason for drug discontinuation. Moreover, cinacalcet therapy can exacerbate oesophago-gastro-duodenal disease in ESRD patients, gastric fluid pH ranging from acid excess to achlorhydria. The aim of our study was to clarify whether the in vitro dissolution of commercially available cinacalcet causes medium pH variations in solutions with different basal proton concentrations, simulating gastric, duodenal and intestinal pH, respectively.