The calcimimetic agents: Perspectives for treatment

• Type: Article in International Scientific Journal
• Date: 2002

Authors

João Frazão (Author) FMUP; Martins, P (Author) Other; Coburn, JW (Author) Other

Journal

Title: Kidney International

Vol. 61

Pages: S149-S154

ISSN: 0085-2538

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 27 Citations

Other information

Authenticus ID: P-000-PJ0

Abstract (EN): The calcimimetic agents: Perspectives for treatment. Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The biology of the low affinity. G-protein-coupled CaR and the effects of its activation in various tissues are reviewed. Physiological roles include regulation of parathyroid hormone (PTH) secretion by small changes in ionized calcium (Ca++), and control of urinary calcium excretion with small chanizes in blood Ca++. The CaR also affects the renal handling of sodium, magnesium, and water. Mutations affecting the CaR that make it either less or more sensitive to Ca++ cause various clinical disorders. Disorders, such as primary and secondary hyperparathyroidism. may exhibit acquired abnormalities of the CaR. Calcimimetic drugs, which amplify the sensitivity of the CaR to Ca++, can suppress PTH levels with a resultant fall in blood Ca++. Experiences with R-568 in patients with secondary and primary hyperparathyroidism and parathyroid carcinoma are summarized. In humans with hyperparathyroidism, these agents produce a dose-dependent fall in PTH and blood Ca++. with larger closes causing more sustained effects. The second generation calcimimetic, AMG 073. with a better pharmacokinetic profile appears to be an effective and safe treatment for secondary hyperparathyroidism, producing suppression of PTH levelswitl a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia. hyper-phosphatemia, and increased calcium X phosphorus product is very promising. Treatment trials have been relatiely short-term except for one patient treated with R-568 for more than 600 days for parathyroid carcinoma; nonetheless the drug had no major side effects and appeared to be safe. Further long-term controlled studies are underway to further confirm the effectiveness and safety of these compounds.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6