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Previous Volume 337:1506-1511 November 20, 1997 Number 21 Next

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ABSTRACT

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 postmenopausal 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 [3.9 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.

Source Information

From the Departments of Medicine (S.J.S., F.G.L., S.T.-J., J.P.B.) and Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York; Henry Ford Hospital, Detroit (H.G.B., S.K.); NPS Pharmaceuticals, Salt Lake City (T.B.M., E.L.S.); and Amgen, Thousand Oaks, Calif. (G.D.).

Address reprint requests to Dr. Silverberg at the Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032.

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