Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism.
BACKGROUND
Uncontrolled hyperparathyroidism (HPT), particularly HPT resulting from chronic kidney disease (CKD), is associated with significant morbidity and cardiovascular mortality. Traditional medical therapy (eg, vitamin D sterols, calcium, phosphate binders) has been inadequate for the management of HPT and its vascular and skeletal complications.


OBJECTIVE
: The goal of this article was to review the efficacy and safety profile of cinacalcet, a second-generation calcimimetic, in the management of HPT secondary to CKD, primary HPT, and parathyroid carcinoma.


METHODS
MEDLINE, Web of Science, and International Pharmaceutical Abstracts were searched from 1995 to July 2005 using the terms cinacalcet, AMG 073, KRN 1493, calcimimetics, hypercalcemia, and hyperparathyroidism.


RESULTS
Compared with placebo, cinacalcet significantly reduced parathyroid hormone levels within 2 to 4 hours after administration (P < 0.05). In Phase III trials involving 1136 patients with secondary HPT, 56% of those who received cinacalcet achieved the National Kidney Foundation Kidney Disease Outcomes Quality Initiative target of a reduction in parathyroid hormone to <300 pg/mL, 65% achieved a calcium-phosphorus product <55 mg2/dL2, and a respective 49% and 46% achieved normalized serum calcium and phosphorus levels (P < 0.001). Cinacalcet's effects were similar regardless of patients' demographic characteristics, duration or mode of dialysis, severity of HPT, or use of concomitant medical therapy. Preliminary evidence suggests that cinacalcet may reverse cortical bone loss. Cinacalcet was well tolerated, with nausea (31%) and vomiting (27%) being the most commonly reported adverse effects. Hypocalcemia was transient in 5% of patients, was usually asymptomatic, and was corrected by dose reduction.


CONCLUSIONS
Based on the available evidence, cinacalcet is effective and well tolerated in the treatment of secondary HPT and refractory parathyroid carcinoma. Its use in primary HPT appears promising. Further investigations are needed to determine if cinacalcet can prevent the long-term complications of HPT and reduce mortality.
Dong
Betty J
BJ
School of Pharmacy, University of California-San Francisco, 521 Parnassus Avenue C-152, San Francisco, CA 94143-0622, USA. dongb@pharmacy.ucsf.edu
D000818:Animals; D019540:Area Under Curve; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000188:drug therapy*; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D016030:Kidney Transplantation; D009281:Naphthalenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D010282:Parathyroid Neoplasms / Q000188:drug therapy*; D010758:Phosphorus / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis
D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium; D000069449:Cinacalcet