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Identification
NameCinacalcet
Accession NumberDB01012  (APRD00872)
TypeSmall Molecule
GroupsApproved
Description

Cinacalcet (INN) is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe. Cinacalcet is used to treat hyperparathyroidism (elevated parathyroid hormone levels), a consequence of parathyroid tumors and chronic renal failure.

Structure
Thumb
Synonyms
(R)-alpha-Methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amine
CNC
Mimpara
N-((1R)-1-(Naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-cinacalcettablet30 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-cinacalcettablet90 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-cinacalcettablet60 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Sensipartablet, coated30 mg/1oralREMEDYREPACK INC.2013-04-01Not applicableUs
Sensipartablet, coated30 mg/1oralAmgen Inc2004-04-04Not applicableUs
Sensipartablet90 mgoralAmgen Canada Inc2004-09-16Not applicableCanada
Sensipartablet, coated60 mg/1oralCardinal Health2004-04-04Not applicableUs
Sensipartablet60 mgoralAmgen Canada Inc2004-09-16Not applicableCanada
Sensipartablet, coated30 mg/1oralCardinal Health2004-04-04Not applicableUs
Sensipartablet30 mgoralAmgen Canada Inc2004-09-16Not applicableCanada
Sensipartablet, coated30 mg/1oralPhysicians Total Care, Inc.2010-03-02Not applicableUs
Sensipartablet, coated30 mg/1oralCarilion Materials Management2004-04-04Not applicableUs
Sensipartablet, coated60 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Sensipartablet, coated90 mg/1oralAmgen Inc2004-04-04Not applicableUs
Sensipartablet, coated30 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Sensipartablet, coated30 mg/1oralAvera Mc Kennan Hospital2015-03-17Not applicableUs
Sensipartablet, coated60 mg/1oralAmgen Inc2004-04-04Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-cinacalcettablet30 mgoralApotex Inc2016-05-20Not applicableCanada
Apo-cinacalcettablet90 mgoralApotex Inc2016-05-20Not applicableCanada
Apo-cinacalcettablet60 mgoralApotex Inc2016-05-20Not applicableCanada
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Cinacalcet hydrochloride
ThumbNot applicableDBSALT001463
Categories
UNIIUAZ6V7728S
CAS number226256-56-0
WeightAverage: 357.412
Monoisotopic: 357.170434324
Chemical FormulaC22H22F3N
InChI KeyInChIKey=VDHAWDNDOKGFTD-MRXNPFEDSA-N
InChI
InChI=1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1
IUPAC Name
[(1R)-1-(naphthalen-1-yl)ethyl]({3-[3-(trifluoromethyl)phenyl]propyl})amine
SMILES
C[C@@H](NCCCC1=CC(=CC=C1)C(F)(F)F)C1=CC=CC2=CC=CC=C12
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassNot Available
Direct ParentNaphthalenes
Alternative Parents
Substituents
  • Phenylpropylamine
  • Naphthalene
  • Aralkylamine
  • Monocyclic benzene moiety
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsCinacalcet 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.
Mechanism of actionThe 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.
Related Articles
AbsorptionRapidly absorbed following oral administration.
Volume of distribution
  • 1000 L
Protein bindingApproximately 93 to 97% bound to plasma proteins.
Metabolism

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.

SubstrateEnzymesProduct
Cinacalcet
Not Available
Hydrocinnamic acidDetails
Cinacalcet
Not Available
hydroxy-hydrocinnamic acidDetails
Route of eliminationCinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2. Renal excretion of metabolites was the primary route of elimination of radioactivity.
Half lifeTerminal 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.
ClearanceNot Available
ToxicityDoses 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9927
Caco-2 permeable+0.7058
P-glycoprotein substrateSubstrate0.5309
P-glycoprotein inhibitor IInhibitor0.8512
P-glycoprotein inhibitor IIInhibitor0.6937
Renal organic cation transporterInhibitor0.5305
CYP450 2C9 substrateNon-substrate0.7761
CYP450 2D6 substrateSubstrate0.8293
CYP450 3A4 substrateNon-substrate0.5425
CYP450 1A2 substrateInhibitor0.9206
CYP450 2C9 inhibitorNon-inhibitor0.8572
CYP450 2D6 inhibitorInhibitor0.8188
CYP450 2C19 inhibitorInhibitor0.8795
CYP450 3A4 inhibitorInhibitor0.7166
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5904
Ames testNon AMES toxic0.5152
CarcinogenicityNon-carcinogens0.8785
BiodegradationNot ready biodegradable0.9932
Rat acute toxicity2.8511 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9175
hERG inhibition (predictor II)Inhibitor0.8494
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Amgen inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral30 mg
Tabletoral60 mg
Tabletoral90 mg
Tablet, coatedoral30 mg/1
Tablet, coatedoral60 mg/1
Tablet, coatedoral90 mg/1
Prices
Unit descriptionCostUnit
Sensipar 90 mg tablet44.03USD tablet
Sensipar 60 mg tablet29.35USD tablet
Sensipar 30 mg tablet14.69USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2202879 No2005-08-302015-10-23Canada
US6011068 No1998-03-082018-03-08Us
US6031003 No1996-12-142016-12-14Us
US6211244 No1995-10-232015-10-23Us
US6313146 No1996-12-142016-12-14Us
US7829595 No2006-09-222026-09-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySlightly soluble (in HCl salt form)Not Available
logP6.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.59e-05 mg/mLALOGPS
logP5.57ALOGPS
logP6.27ChemAxon
logS-6.8ALOGPS
pKa (Strongest Basic)10.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity100.12 m3·mol-1ChemAxon
Polarizability37.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Revital Lifshitz-Liron, “Process for the preparation of cinacalcet base.” U.S. Patent US20070259964, issued November 08, 2007.

US20070259964
General References
  1. Torres PU: Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr. 2006 Jul;16(3):253-8. [PubMed:16825031 ]
  2. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  3. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
External Links
ATC CodesH05BX01
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (278 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Cinacalcet.
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Cinacalcet.
AprepitantThe serum concentration of Cinacalcet can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Cinacalcet.
AtomoxetineThe serum concentration of Atomoxetine can be increased when it is combined with Cinacalcet.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Cinacalcet.
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Cinacalcet.
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Cinacalcet.
ConivaptanThe serum concentration of Cinacalcet can be increased when it is combined with Conivaptan.
DasatinibThe serum concentration of Cinacalcet can be increased when it is combined with Dasatinib.
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Cinacalcet.
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Cinacalcet.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Cinacalcet.
DuloxetineThe serum concentration of Duloxetine can be increased when it is combined with Cinacalcet.
EliglustatThe serum concentration of Eliglustat can be increased when it is combined with Cinacalcet.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Cinacalcet.
FluconazoleThe metabolism of Cinacalcet can be decreased when combined with Fluconazole.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Cinacalcet.
FosaprepitantThe serum concentration of Cinacalcet can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Cinacalcet can be increased when it is combined with Fusidic Acid.
HydrocodoneThe serum concentration of the active metabolites of Hydrocodone can be reduced when Hydrocodone is used in combination with Cinacalcet resulting in a loss in efficacy.
IdelalisibThe serum concentration of Cinacalcet can be increased when it is combined with Idelalisib.
IloperidoneThe serum concentration of the active metabolites of Iloperidone can be increased when Iloperidone is used in combination with Cinacalcet.
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Cinacalcet.
IvacaftorThe serum concentration of Cinacalcet can be increased when it is combined with Ivacaftor.
LuliconazoleThe serum concentration of Cinacalcet can be increased when it is combined with Luliconazole.
MequitazineThe serum concentration of Mequitazine can be increased when it is combined with Cinacalcet.
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Cinacalcet.
MifepristoneThe serum concentration of Cinacalcet can be increased when it is combined with Mifepristone.
NebivololThe serum concentration of Nebivolol can be increased when it is combined with Cinacalcet.
NelfinavirThe metabolism of Cinacalcet can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Cinacalcet can be increased when it is combined with Netupitant.
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Cinacalcet.
PalbociclibThe serum concentration of Cinacalcet can be increased when it is combined with Palbociclib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Cinacalcet.
PropafenoneThe serum concentration of Propafenone can be increased when it is combined with Cinacalcet.
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Cinacalcet.
SimeprevirThe serum concentration of Cinacalcet can be increased when it is combined with Simeprevir.
StiripentolThe serum concentration of Cinacalcet can be increased when it is combined with Stiripentol.
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Cinacalcet.
TamoxifenThe serum concentration of the active metabolites of Tamoxifen can be reduced when Tamoxifen is used in combination with Cinacalcet resulting in a loss in efficacy.
TamsulosinThe serum concentration of Tamsulosin can be increased when it is combined with Cinacalcet.
TetrabenazineThe serum concentration of Tetrabenazine can be increased when it is combined with Cinacalcet.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Cinacalcet.
TramadolThe therapeutic efficacy of Tramadol can be decreased when used in combination with Cinacalcet.
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Cinacalcet.
VortioxetineThe serum concentration of Vortioxetine can be increased when it is combined with Cinacalcet.
Food Interactions
  • Food markedly increases product bioavailability.
  • 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.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
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.
Gene Name:
CASR
Uniprot ID:
P41180
Molecular Weight:
120672.385 Da
References
  1. de Francisco AL: Cinacalcet HCl: a novel therapeutic for hyperparathyroidism. Expert Opin Pharmacother. 2005 Mar;6(3):441-52. [PubMed:15794735 ]
  2. 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. [PubMed:15864123 ]
  3. Tasic V: Management of renal osteodystrophy in children. Turk J Pediatr. 2005;47 Suppl:13-8. [PubMed:15884662 ]
  4. 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. [PubMed:16030053 ]
  5. Cunningham J: Management of secondary hyperparathyroidism. Ther Apher Dial. 2005 Aug;9 Suppl 1:S35-40. [PubMed:16109140 ]
  6. 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. [PubMed:19461861 ]
  7. 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. doi: 10.2215/CJN.03790808. Epub 2009 Mar 4. [PubMed:19261825 ]
  8. 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. doi: 10.1093/ndt/gfn654. Epub 2009 Jan 30. [PubMed:19181759 ]
  9. 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. doi: 10.2215/CJN.04520908. Epub 2008 Dec 3. [PubMed:19056615 ]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. [PubMed:19566113 ]
  2. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. [PubMed:16368445 ]
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Drug created on June 13, 2005 07:24 / Updated on July 24, 2016 01:52