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QuickView for Cinacalcet (compound)

Summary
General Info

PubChem

PubChem Compound 156418

Name:	cinacalcet
PubChem Compound ID:	156418
Molecular formula:	C₂₂H₂₃ClF₃N
Molecular weight:	393.873 g/mol
Synonyms:	KRN-1493; 364782-34-3; 226256-56-0; N-((1R)-1-(Naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride; AMG-073; Cinacalcet hydrochloride; Mimpara; AMG073 HCl; Cinacalcet hydrochloride (JAN/USAN); D03505. show more » KRN-1493; 364782-34-3; 226256-56-0; N-((1R)-1-(Naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride; AMG-073; Cinacalcet hydrochloride; Mimpara; AMG073 HCl; Cinacalcet hydrochloride (JAN/USAN); D03505; NPS-1493; Parareg; Cinacalcet hydrochloride [USAN]; Sensipar (TN); Sensipar; 1-Naphthalenemethanamine, a-methyl-N-(3-(3-(trifluoromethyl)phenyl)propyl)-, (aR)-, hydrochloride; AMG-073.HCl show less «

DrugBank

Identification

Name:	cinacalcet
Name (isomeric):	DB01012
Drug Type:	small molecule
Brand:	Sensipar
Category:	Calcimimetics
CAS number:	226256-56-0

Pharmacology

Indication:	For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who are on hemodialysis or peritoneal dialysis. Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.
Pharmacology:	Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates ... show more » Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium. show less «
Mechanism of Action:	The calcium-sensing receptors on the surface of the chief cell of the parathyroid gland is the principal regulator of parathyroid hormone secretion (PTH). Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH sec... show more » The calcium-sensing receptors on the surface of the chief cell of the parathyroid gland is the principal regulator of parathyroid hormone secretion (PTH). Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels. show less «
Absorption:	Rapidly absorbed following oral administration.
Protein binding:	Approximately 93 to 97% bound to plasma proteins.
Biotransformation:	Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolized via: 1) oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which are further metabolized via ß-oxidation and glycine conjugation; the oxidative N-dealkylation process also generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the parent drug to form dihydrodiols, which are further conjugated with glucuronic acid.
Route of elimination:	Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2. Renal excretion of metabolites was the primary route of elimination of radioactivity.
Half Life:	Terminal half-life is 30 to 40 hours. The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
Toxicity:	Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of cinacalcet may lead to hypocalcemia.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Peak levels and area under curve (drug exposure) are increased (82% and 68% respectively) when product is taken with a lipid-rich meal.

Take with food or soon after a meal.

Food markedly increases product bioavailability.

Drug interaction:

Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cinacalcet by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cinacalcet if voriconazole is initiated, discontinued or dose changed.
Erythromycin	The macrolide, erythromycin, may increase the serum concentration and toxicity of cinacalcet.
Tolterodine	Cinacalcet may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
Ketoconazole	Ketoconazole may increase the effect and toxicity of cinacalcet.
Telithromycin	Telithromycin may reduce clearance of Cinacalcet. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Cinacalcet if Telithromycin is initiated, discontinued or dose changed.

Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cinacalcet by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cinacalcet if voriconazole is initiated, discontinued or dose changed.
Erythromycin	The macrolide, erythromycin, may increase the serum concentration and toxicity of cinacalcet.
Tolterodine	Cinacalcet may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
Ketoconazole	Ketoconazole may increase the effect and toxicity of cinacalcet.
Telithromycin	Telithromycin may reduce clearance of Cinacalcet. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Cinacalcet if Telithromycin is initiated, discontinued or dose changed.
Zuclopenthixol	Cinacalcet, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if cinacalcet is initiated, discontinued or dose changed.
Trimipramine	The strong CYP2D6 inhibitor, Cinacalcet, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Cinacalcet is initiated, discontinued or dose changed.
Tamsulosin	Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cinacalcet is initiated, discontinued, or dose changed.
Itraconazole	Itraconazole may increase the effect and toxicity of cinacalcet.
Venlafaxine	Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cinacalcet is initiated, discontinued, or dose changed.
Tramadol	Cinacalcet may decrease the effect of Tramadol by decreasing active metabolite production.
Tamoxifen	Cinacalcet may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.

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Targets

Extracellular calcium-sensing receptor

Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G- protein that activates a phosphatidylinositol-calcium second messenger system

UniProt ID:

P41180

Gene:

CASR

Actions:

agonist

References:

de Francisco AL: Cinacalcet HCl: a novel therapeutic for hyperparathyroidism. Expert Opin Pharmacother. 2005 Mar;6(3):441-52.
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Rothe HM, Shapiro WB, Sun WY, Chou SY: Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on response to cinacalcet HCl. Pharmacogenet Genomics. 2005 Jan;15(1):29-34.
View Article

Tasic V: Management of renal osteodystrophy in children. Turk J Pediatr. 2005;47 Suppl:13-8.
View Article

Moe SM, Cunningham J, Bommer J, Adler S, Rosansky SJ, Urena-Torres P, Albizem MB, Guo MD, Zani VJ, Goodman WG, Sprague SM: Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Nephrol Dial Transplant. 2005 Oct;20(10):2186-93. Epub 2005 Jul 19.
View Article

Cunningham J: Management of secondary hyperparathyroidism. Ther Apher Dial. 2005 Aug;9 Suppl 1:S35-40.
View Article

Eriguchi R, Umakoshi J, Tominaga Y, Sato Y: Successful treatment of inoperable recurrent secondary hyperparathyroidism with cinacalcet HCl. NDT Plus. 2008 Aug;1(4):218-220. Epub 2008 May 25.
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Belozeroff V, Goodman WG, Ren L, Kalantar-Zadeh K: Cinacalcet lowers serum alkaline phosphatase in maintenance hemodialysis patients. Clin J Am Soc Nephrol. 2009 Mar;4(3):673-9. Epub 2009 Mar 4.
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Meola M, Petrucci I, Barsotti G: Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism. Nephrol Dial Transplant. 2009 Mar;24(3):982-9. Epub 2009 Jan 30.
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Drueke TB, Ritz E: Treatment of secondary hyperparathyroidism in CKD patients with cinacalcet and/or vitamin D derivatives. Clin J Am Soc Nephrol. 2009 Jan;4(1):234-41. Epub 2008 Dec 3.
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Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
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Enzymes

Cytochrome P450 3A4

Cytochrome P450 2D6

Cytochrome P450 1A2