Calcimimetics increase the sensitivity of the
calcium-sensing receptor (CaR) to circulating serum
calcium, reducing the secretion of PTH and the serum
calcium concentration. We evaluated the calcimimetic
cinacalcet, a novel
therapy for the management of
primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with
primary hyperparathyroidism were given
cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum
calcium, plasma PTH, and 24-h and fasting urine
calcium were measured. Baseline mean serum
calcium was 10.6 mg/dl for the combined
cinacalcet-treated patients (normal range, 8.4-10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10-65 pg/ml) for the combined
cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum
calcium normalized after the second dose on d 1 and remained normal through d 15 in all
cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2-4 h after dosing in all
cinacalcet-treated groups. The fasting and 24-h urine
calcium to
creatinine ratios were similar in the
cinacalcet and placebo groups. This study demonstrates that
cinacalcet safely normalized serum
calcium and lowered PTH concentrations without increasing urinary
calcium excretion in the study subjects, indicating the potential benefit of
cinacalcet as a medical treatment for
primary hyperparathyroidism.