The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

• Published in: The journal of clinical endocrinology and metabolism Vol. 88; no. 12; pp. 5644 - 5649
• Main Authors: Shoback, Dolores M., Bilezikian, John P., Turner, Stewart A., McCary, Laura C., Guo, Matthew D., Peacock, Munro
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.12.2003; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Aged; Biological and medical sciences; Calcium (urinary); Calcium - blood; Calcium - urine; Cinacalcet Hydrochloride; Creatinine; Dosage; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Endocrinopathies; Fasting; Female; Hormones. Endocrine system; Humans; Hyperparathyroidism; Hyperparathyroidism - blood; Hyperparathyroidism - drug therapy; Hyperparathyroidism - urine; Male; Medical sciences; Medical treatment; Middle Aged; Naphthalenes - administration & dosage; Naphthalenes - adverse effects; Naphthalenes - therapeutic use; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Osmolar Concentration; Parathyroid hormone; Parathyroid Hormone - blood; Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases); Patients; Pharmacology. Drug treatments; Placebos; Time Factors; Endocrinopathy; Human; Urine; Treatment efficiency; Blood plasma; Chemotherapy; Randomization; Calcium ion; Treatment; Parathyroid diseases; Parathyroid hormone; Double blind study; Cinacalcet; Hyperparathyroidism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021597

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.