Short-term inhibition of parathyroid hormone secretion by a calcium- receptor agonist in patients with primary hyperparathyroidism

Background: Surgery is the usual therapy for patients with primary hyperparathyroidism. We investigated the ability of a calcimimetic drug that inhibits parathyroid hormone secretion in vitro to decrease serum parathyroid hormone and calcium concentrations in patients with this disorder. Methods: We performed a randomized, placebo-controlled study of single oral doses of 4 to 160 mg of the calcium-receptor agonist drug R-568 in 20 post-menopausal women with mild primary hyperparathyroidism. At base line, the mean (±SE) serum calcium concentration was 10.7±0.2 mg per deciliter (2.67±0.05 mmol per liter). Serum parathyroid hormone and calcium were measured repeatedly after each dose, and safety was assessed. Results: Administration of R-568 resulted in a dose-dependent inhibition of parathyroid hormone secretion. The mean serum parathyroid hormone concentration, which was 77±11 pg per milliliter (18.8±2.7 pmol per liter; normal range, 16 to 65 pg per milliliter [13.9 to 15.9 pmol per liter]) at base line, fell by 26±8 percent after 20 mg of R-568 (P= 0.03), by 42±7 percent after 80 mg (P=0.01), and by 51±5 percent after 160 mg (P=0.005). Serum ionized calcium concentrations fell only after the 160-mg dose, with the decrease closely following the decrease in the serum parathyroid hormone concentration. Conclusions: The calcimimetic drug R-568 reduces serum parathyroid hormone and ionized calcium concentrations in postmenopausal women with primary hyperparathyroidism.