Cinacalcet: Pharmacological and clinical aspects

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 12, 2008, Pages 1551-1560

  Messa, Piergiorgio ^a   Alfieri, Carlo ^a   Brezzi, Brigida ^a  

^a FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

Author keywords

Calcimimetrics; Calcium sensing receptor; Parathyroid hormone; Secondary hyperparathyroidism

Indexed keywords

CALCIUM; CALCIUM SENSING RECEPTOR; CINACALCET; CYTOCHROME P450 1A2; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DEXTROMETHORPHAN; ERYTHROMYCIN; FLECAINIDE; ITRACONAZOLE; KETOCONAZOLE; PARATHYROID HORMONE; PHOSPHATE; PHOSPHATE BINDING AGENT; PLACEBO; THIORIDAZINE; TRICYCLIC ANTIDEPRESSANT AGENT; VINBLASTINE; VITAMIN D;

ARTICLE; BINDING AFFINITY; BIOCHEMISTRY; CALCIUM TRANSPORT; CELL PROLIFERATION; CHRONIC KIDNEY FAILURE; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; ENZYME INHIBITION; GASTROINTESTINAL DISEASE; HEMODIALYSIS; HORMONE RELEASE; HUMAN; HYPOCALCEMIA; INHIBITION KINETICS; KIDNEY TRANSPLANTATION; MAXIMUM PLASMA CONCENTRATION; MEDICAL RESEARCH; MULTIPLE ENDOCRINE NEOPLASIA; NAUSEA AND VOMITING; PARATHYROID CELL; PARATHYROID HORMONE RELEASE; PERITONEAL DIALYSIS; PRIMARY HYPERPARATHYROIDISM; PROTEIN EXPRESSION; RECEPTOR UPREGULATION; SECONDARY HYPERPARATHYROIDISM; TREATMENT OUTCOME;

CALCIUM; CLINICAL TRIALS AS TOPIC; COST-BENEFIT ANALYSIS; HUMANS; HYPERPARATHYROIDISM; NAPHTHALENES; PARATHYROID HORMONE; RECEPTORS, CALCIUM-SENSING; TREATMENT OUTCOME;

EID: 58149181574     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425250802587017     Document Type: Article

References (93)

1. Silverberg SJ, Shane E, Jacobs TP, et al. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 1999;341:1249-55
2. Weigel RJ. Nonoperative management of hyperparathyroidism: present and future. Curr Opin Oncol 2001;13:33-8
3. Drüeke T. The pathogenesis of parathyroid gland hyperplasia in chronic renal failure nephrology forum 1995;48:259-72
4. Malluche H, Faugere MC. Renal bone disease 1990: an unmet challenge for the nephrologists. Kidney Int 1990;38:193-211
5. Amann K, Ritz E, Wiest G, et al. A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol 1994;4:1814-9
6. Amann K, Ritz E. Cardiac disease in chronic uremia: pathophysiology. Adv Ren Replace Ther 1997;4:212-24
7. Vaziri ND, Wang XQ, Liang K. Secondary hyperparathyroidisin downregulates lipoprotein lipase expression in chronic renal failure. Am J Physiol 1997;273:F925-30
8. Fadda GZ, Hajjar SM, Perna AF, et al. On the mechanism of impaired insulin secretion in chronic renal failure. J Clin Invest 1991;87:255-61
9. Ganesh SK, Stack AG, Levin NW. et al. Association of elevated serum PO4, Ca x PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001;12:2131-8
10. Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J kidney Dis 2000;35:1226-37
11. Block G, Port FK. Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease. Semin Dial 2003;16:140-7
12. National Kidney Foundation: K/DOQI clinical practice guidelines on bone metabolism and disease. Am J Kidney Dis 2003;42(S3):1-201
13. Andress DL, Norris KC, Coburn JW, et al. Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N Engl J Med 1989;321:274-9
14. Martin KJ, Gonzalez EA, Gellens M, et al. 19-nor-1-a-25-dihydroxyvitamin D2(paricalcitol) safely and effectively reduces the levels of PTH in patients with hemodialysis. J Am Soc Nephrol 1998;9:1427-32
15. Goodman WG. Recent developments in the management of secondary hyperparathyroidism. Kidney Int 2001;59:1187-201
16. Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005;67:1179-87
17. Ringer S. A further contribution regarding the influence of different constituents of the blood on the contraction of the heart. J Physiol 1883;4:29-43
18. Shoback DM, Thatcher J, Leombruno R, Brown EM. Relationship between parathyroid hormone secretion and cyrosolic calcium concentration in dispersed bovine parathyroid cells. Proc Natl Acad Sci USA 1984;81:3113-7
19. Brown EM. Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messenger. Physiol Rev 1991;71:371-411
20. Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an exEracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993;366:575-80
21. Brown EM, Vassilev PM, Quinn S, Hebert SC. G-protein-coupled, extracellular Ca(2+)-sensing receptor: a versatile regulator of diverse cellular functions. Vitam Horm 1999;55:1-71
22. Chang W, Shoback D. Extracellular Ca2+ sensing receptors - an overview. Cell Calcium 2004;35:183-96
23. Breitwieser GE, Miedlich SU, Zhang M. Calcium sensing receptors as integrators of multiple metabolic signals. Cell Calcium 2004;35:209-16
24. Bai M. Structure-function relationship of the extracellular calcium-sensing receptor. Cell Calcium 2004;35:197-207
25. Coburn JW, Elangovan L, Goodman WG, Frazao JM. Calcium-sensing receptor and calcimimetic agents. Kidney Int 1999;S73:52-8
26. Ward Donald T. Calcium receptor-mediated intracellular signalling Cell Calcium 2004;35:217-28
27. Brown EM. Calcium receptor and regulation of parathyroid hormone secretion. Rev Endocr Metab Dis 2000;1:307-15
28. Ba Jianming, Friedman Peter A. Calcium-sensing receptor regulation of renal mineral ion transport. Cell Calcium 2004;35:229-37
29. Dvorak MM, Riccardi D. Ca(2+) as an extracellular signal in bone. Cell Calcium 2004;35:249-55
30. Pi M, Quarles LD. Osteoblast Calcium-Sensing Receptor has characteristics of ANF/7TM receptors. J Cell Biochem 2005;95:1081-92
31. Hebert SC, Cheng S, Geibel J. Functions and roles of the extracellular Ca(2+)-sensing receptor in the gastrointestinal tract. Cell Calcium 2004;35:239-47
32. Thakker RV. Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium 2004;35:275-82
33. Brown EM. Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. J Clin Endocrinol Metab 1983;56:572-81
34. Cetani F, Picone A, Cerrai P, et al. Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 2000;85(12):4789-94
35. Gogusev J, Duchambon P, Hory B, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997;51:329-36
36. Brown EM, Wilson RE, Eastman RC, et al. Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. J Clin Endocrinol Metab 1982;54:172-9
37. Brown AJ, Ritter CS, Finch JL, Slatopolsky EA. Decreased calcium-sensing receptor extression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int 1999;55:1284-92
38. Malberti F, Faina M, Imbasciati E. The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism. Nephrol Dial Transplant 1999; 14:2398-406
39. Messa P, Vallone C, Mioni G, et al. Direct in vivo assessment of parathyroid hormone-calcium relationship curve in renal patients. Kidney Int 1994;46:1713-20
40. Nemeth E, Fox I. Calcimimetics compounds: a direct approach to controlling plasma levels of parathyroid hormone in hyperparathyroidism. Trends Endocrinol Metab 1999;10:66-71
41. Nemeth EF, Steffey ME, Hammerland LG, et al. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci USA 1998;95:4040-5
42. Antonsen JE, Sherrard DJ, Andress DL. A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication. Kidney Int 1998;53:223-7
43. Goodman WG, Frazao JM, Goodkin DA, et al. A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney Int 2000;58:436-45
44. Nemeth EF, Heaton WH, Miller M, et al. Pharmacodynamics of the type II calcimetic compound cinacalcet HCI. J Pharmacol Exp Ther 2004;308:627-35
45. Kumar GN, Sproul C, Poppe L, et al. Metabolism and disposition of calcimimetic agent cinacalcet HC1 in humans and animal models. Drug Metab Dispos 2004;32:1491-500
46. Harris RZ, Padhi D, Marbury TC, et al. Pharmacokinetics, pharmacodynamic, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. Am J Kidney Dis 2004;44:1070-6
47. Rothe HM, Shapiro WB, Sun WY, Chou SY. Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on response to cinacalcet HC1. Pharmacogenet Genomics 2005;15:29-34
48. Amgen Inc. Cinacalcet (Sensipar) US prescribing information [online]. URL: Available from: http://www.sensipar.com
49. Padhi D, Salfi M, Harris RZ. The Pharmacokinetics of Cinacalcet are unaffected following consumption of high- and low-fat meals. Am J Ther 2007;14:235-40
50. Balfour JAB, Scott LJ. Cinacalcet Hydrochloride. Drugs 2005;65:271-81
51. Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HC1, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol 2005;16:800-7
52. Serra AL, Braun SC, Starke A, et al. Pharmacokinerics and Pharmacodynamics of Cinacalcet in patients with hyperparathyroidism after renal transplantation. Am J Transplant 2008;8:803-10
53. Nakashima D, Takama H, Ogasawara Y, et al. Effect of cinacalcer hydrochloride, a new calcimimetic agent, on the pharmacokinetics of destromethorphan: in vitro and clinical studies. J Clin Pharmacol 2007;47:1311-9
54. Evenepoel P. calcimimetics in chronic kidney disease: evidence, opportunities and challenges. Kidney Int 2008;74:265-75
55. Shoback DM, Bilezikian JP, Turner SA, et al. The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism. J Clin Endocrinol Metab 2003;88:5644-9
56. Peacock M, Bilezikian JP, Klassens PS, et al. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 2005;90:135-41
57. Silverberg SJ, Rubin MR, Faiman C, et al. Cinacalcet hydrochloride reduces the serum calcium concentration in inperable parathyroid carcinoma. J Clin Endocrinol Metab 2007;92:3803-8
58. Sajid-Crocket S, Singer FR, Hershman JM. Cinacalcer for the treatment of primary hyperparathyroidism. Metabolism 2008;57:517-21
59. Iglesias P, Ais G, Gonzalez A, et al. Acute and one-year effects of cinacalcet in patients with persistent primary hyperparathyroidism after unsuccessful parathyroidectomy. Am J Med Sci 2008;335:111-4
60. Falchetti A, Cilotti A, Vaggelli L, et al. A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet. Nat Clin Pract Endocrinol Metab 2008;4:351-7
61. Goodman WG, Hladik GA, Turner SA, et al. The calcimimetic agent AMG 073 lowers plasma hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 2002;13:1017-24
62. Quarles LD, Sherrard DJ, Adler S, et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003;14:575-83
63. Lindberg JS, Moe SM, Goodman WG, et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 2003
64. Block GA, Martin KJ, De Francisco ALM, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004;350:1516-25
65. Moe SM, Cunningham J, Bommer J, et al. Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCI. Nephrol Dial Transplant 2005;20:2186-93
66. Messa P, Macario F, Yagoob M, et al. The optima study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol 2008;3:36-45
67. Strippoli GFM, Palmer S, Tong A, et al. Meta-analysis of biochemical and patient-level effects of calcimimetic therapy. Am J Kidney Dis 2006;47:715-26
68. Malluche HH, Moner-Faugere MC, Wang G, et al. An assessment of cinacalcet HCI effects on bone histology i dialysis patients with secondary hyperparathyroidism. Clin Nephrol 2008;69:269-77
69. Lien YHH, Silva AL, Whittman D. Effects of Cinacalcet on bone mineral density in patients with secondary hyperparathyroidism. Nephrol Dial Transplant 2005;20:1232-7
70. Ureña Torres P. Clinical experience with cinacalcet HC1. Nephrol Dial Transplant 2004;19(Suppl 5):v27-33
71. Cunningham J, Danese M, Olson K, et al. Effects of the calcimimetic cinacalcer HC1 on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005;68:1793-800
72. Shalhoub V, Shatzen E, Henley C, et al. Calcificacion inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols. Calcif Tissue Int 2006;79:431-42
73. Lopez J, Mendoza FJ, Agulera-Tejero E, et al. The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats. Kidney Int 2008;73:300-7
74. Messa P, Alberti L, Como G, et al. Calcimimetic increases osteoprotegerin and decreases fetuin-A levels in dialysis patients. Nephrol Dial Transplant 2007;22:2724-5
75. Chertow GM, Pupim LB, Block GA, et al. Evaluation of Cinacaclet therapy to lower cardiovascular events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol 2007;2:898-905
76. Charytan C, Coburn JW, Chonchol M, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis 2005;46:58-67
77. Kestenbaum B, Sampson JN, Rudser KD, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16:520-8
78. De Francisco ALM, Pinera C, Palomar R. Cinacalcet should be used to treat secondary hyperparathyroidism in stage 3-4 chronic kidney disease. Nat Clin Pract [Online pub 27 May 2008]
79. Coyne DW. Cinacalcet should not be used to treat secondary hyperparathyroidism in stage 3-4 chronic kidney disease. Nat Clin Pract [Online pub 13 May 2008]
80. Messa P, Sindici C, Cannella G, et al. Persistent secondary hyperparathyroidism after renal transplantation. Kidney Int 1998;54:1704-13
81. Evenepoel P, Claes K, Kuypers D, et al. Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single centre study. Nephrol Dial Transplant 2004;19:1281-7
82. Gwinner W, Suppa S, Mengel M, et al. Early calcification of renal allografts detected by protocol biopsies: causes and clinical implications. Am J Transplant 2005;5:1934-41
83. Serra AL, Schwarz AA, Wick FH, et al. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant 2006;21:1736
84. Szwarc I, Argilés A, Garrigue V, et al. Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism. Transplantation 2006;82:675-80
85. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant 2007;22:2362-5
86. Falck P, Vethe NT, Asberg A, et al. Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients. Nephrol Dial Transplant 2008;23:1048-53
87. Peng LW, Logan JL, James SH, et al. Cinacalcet-associated graft dysfunction and nephrocalcinosis in a kidney transplant recipient. Am J Med 2007;120:e7-9
88. Mohammed IA, Sekar V, Bubtana AJ, et al. Proximal calciphylaxis treated with calcimimetic 'Cinacalcet'. Nephrol Dial Transplant 2008;23:387-9
89. Colloton M, Shatzen E, Miller G, et al. Cinacalcet HC1 attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int 2005;67:467-76
90. Pattaragarn A, Foz J, Alon US. Effect of the calcimimeticNPS R-467 on furosemide-induced nephrocalcinosis in the young rat. Kidney Int 2004;65:1684-9
91. Piecha G, Kokeny G, Nakagawa K, et al. Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats. Am J Physiol Renal Physiol 2008;294:F748-57
92. Garside R, Pitt M, Anderson R, et al. The cost-utility of cinacalcet in addition to standard care compared to standard care alone for secondary hyperparathyroidism in end-stage renal disease: a UK perspective. Nephrol Dial Transplant 2007;22:1428-36
93. Narayan R, Perkins RM, Berbano EP, et al. Parathyroidectomy versus cinacalcet hydrochloride-based medical therapy in the management of hyperparathyroidism in ESRD: a cost utility analysis. Am J Kidney Dis 2007;49:801-13.