Human calcitonin

Identification

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Name
Human calcitonin
Accession Number
DB06773
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Description

Calcitonin was first discovered in isolated parathyroid tissue as a substance with a serum-calcium-lowering effect.2 It is constituted as a 32-amino acid single chain polypeptide structure that gets secreted as a regulatory agent in calcium-phosphorus metabolism.1 It is used as an alternative for people developing antibodies against salmon calcitonin.3

Protein structure
Db06773
Protein chemical formula
C151H226N40O45S3
Protein average weight
3417.9 Da
Sequences
>>>Human calcitonin<<<<
CGNLSTCMLGTYTQDFNKFHTFPQTAIGVGAP
Download FASTA Format
Synonyms
  • Calcitonin (human synthetic)
  • Calcitonin (human)
  • Calcitonin human
  • Calcitonin, human
  • Calcitonin, human synthetic
External IDs
BA-47175
Categories
UNII
I0IO929019
CAS number
21215-62-3

Pharmacology

Indication

Human calcitonin is indicated for the treatment of Paget's disease in the cases where the use of salmon calcitonin may provoke the generation of high-titer of antibodies.3 Paget's disease is a metabolic bone disorder characterized by focal areas of increased and disorganized bone turnover coupled with an increased bone formation. The majority of the cases are asymptomatic but some clinical manifestations include pain, bone deformity and some complications such as pathological fractures and deafness.4 The increased activity in bone is associated with a rise in serum level of alkaline phosphatase and the increased urinary excretion of hydroxyproline which is a product of bone breakdown.2

Pharmacodynamics

Administration of human calcitonin has shown to increase bone calcium content and reduce the levels of serum calcium and serum phosphorus. This calcium inhibition leads to decreases in urinary calcium, magnesium and urine hydroxyproline. Some reports indicate a calcitonin-driven reduction of phosphate plasma concentration which is thought to be related to increased excretion of phosphate. Calcitonin can increase excretion of calcium, phosphate, and sodium. It also is proven to induce the appearance of normal lamellar bone against the diseased trabeculae and a striking decrease in the number of osteoclasts. Bone pain tends to be relieved within a few weeks, and it does not present an important effect on normal bone.3 It is important to point out that human calcitonin is less active than the salmon calcitonin. This characteristic happens because of a high tendency to aggregate, and thus, human calcitonin is used just in cases where the usage of salmon calcitonin generated the formation of antibodies.5 For this reason, the use of human calcitonin is only indicated when there is the appearance of a high-titer of antibodies anti-salmon calcitonin because these antibodies are suggested to cause a relapse.3

Mechanism of action

Calcitonin inhibits osteoclast-mediated bone resorption through the regulation of the number and activity of osteoclasts.1 The action of human calcitonin on osteoclasts is due to a disruption of cytoskeletal organization, by the distraction of actin rings, and due to a disappearance of the cellular polarity of osteoclasts. At the subcellular level, calcitonin is suggested to perform its activity by the modulation of the cAMP-PKA signaling pathway.6

TargetActionsOrganism
AAlpha-actinin-1
incorporation into and destabilization
Humans
Absorption

The human calcitonin tends to aggregate irreversibly forming amyloid fibrils. This property compromises the bioavailability and therapeutic activity of exogenous human calcitonin.5 When human calcitonin reaches the intestine, by intracolonic administration, it is absorbed within minutes and it is distributed intact in plasma. The level of absorption is low and the bioavailability can range from 0.01-2.7%.7

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

The kidneys account for two-thirds of the metabolism of calcitonin and generate low molecular weight forms. At a subcellular level, it has been observed the metabolic activity of N-acetyl-beta-glucosaminidase, alanyl aminopeptidase, and phosphoglucomutase.10

Route of elimination
Not Available
Half life

Intravenous administration of human calcitonin presents a half-life in the range of 10.2-37.8 min.8

Clearance

The metabolic secretion rate is in the range of 6-9 ml/min.kg while the secretion rate is 59 ng/dl.kg for men and 22 ng/dl.kg for women.9 The total renal clearance of human calcitonin is 1.96 ml/min. The renal clearance exceeds the glomerular filtration rate which indicates a filtration-independent removal.10

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Alendronic acidThe risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Alendronic acid.
Clodronic acidThe risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Clodronic acid.
Etidronic acidThe risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Etidronic acid.
IbandronateThe risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Ibandronate.
Incadronic acidThe risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Incadronic acid.
Lithium carbonateHuman calcitonin may increase the excretion rate of Lithium carbonate which could result in a lower serum level and potentially a reduction in efficacy.
Lithium cationHuman calcitonin may increase the excretion rate of Lithium cation which could result in a lower serum level and potentially a reduction in efficacy.
Lithium citrateHuman calcitonin may increase the excretion rate of Lithium citrate which could result in a lower serum level and potentially a reduction in efficacy.
Lithium hydroxideHuman calcitonin may increase the excretion rate of Lithium hydroxide which could result in a lower serum level and potentially a reduction in efficacy.
Lithium succinateHuman calcitonin may increase the excretion rate of Lithium succinate which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Arvinte T, Drake AF: Comparative study of human and salmon calcitonin secondary structure in solutions with low dielectric constants. J Biol Chem. 1993 Mar 25;268(9):6408-14. [PubMed:8454613]
  2. Authors unspecified: Clinical applications of calcitonin. Can Med Assoc J. 1971 Aug 7;105(3):238-9. [PubMed:5563336]
  3. Authors unspecified: Editorial: Paget's disease and calcitonin. Br Med J. 1975 Aug 30;3(5982):505-6. [PubMed:1164607]
  4. Alonso N, Calero-Paniagua I, Del Pino-Montes J: Clinical and Genetic Advances in Paget's Disease of Bone: a Review. Clin Rev Bone Miner Metab. 2017;15(1):37-48. doi: 10.1007/s12018-016-9226-0. Epub 2016 Dec 19. [PubMed:28255281]
  5. Fowler SB, Poon S, Muff R, Chiti F, Dobson CM, Zurdo J: Rational design of aggregation-resistant bioactive peptides: reengineering human calcitonin. Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10105-10. doi: 10.1073/pnas.0501215102. Epub 2005 Jul 8. [PubMed:16006528]
  6. Yamamoto Y, Noguchi T, Takahashi N: [Effects of calcitonin on osteoclast]. Clin Calcium. 2005 Mar;15(3):147-51. doi: CliCa0503467471. [PubMed:15741694]
  7. Beglinger C, Born W, Muff R, Drewe J, Dreyfuss JL, Bock A, Mackay M, Fischer JA: Intracolonic bioavailability of human calcitonin in man. Eur J Clin Pharmacol. 1992;43(5):527-31. [PubMed:1483490]
  8. Antonin KH, Saano V, Bieck P, Hastewell J, Fox R, Lowe P, Mackay M: Colonic absorption of human calcitonin in man. Clin Sci (Lond). 1992 Nov;83(5):627-31. [PubMed:1335402]
  9. Tiegs RD, Body JJ, Barta JM, Heath H 3rd: Secretion and metabolism of monomeric human calcitonin: effects of age, sex, and thyroid damage. J Bone Miner Res. 1986 Aug;1(4):339-49. doi: 10.1002/jbmr.5650010407. [PubMed:3503547]
  10. Simmons RE, Hjelle JT, Mahoney C, Deftos LJ, Lisker W, Kato P, Rabkin R: Renal metabolism of calcitonin. Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600. doi: 10.1152/ajprenal.1988.254.4.F593. [PubMed:2833122]
External Links
PubChem Substance
347910370
Wikipedia
Calcitonin
ATC Codes
H05BA03 — Calcitonin (human synthetic)
MSDS
Download (22.1 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1 mg/ml'MSDS'

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Incorporation into and destabilization
General Function
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
Specific Function
Actin filament binding
Gene Name
ACTN1
Uniprot ID
P12814
Uniprot Name
Alpha-actinin-1
Molecular Weight
103056.695 Da
References
  1. Beglinger C, Born W, Muff R, Drewe J, Dreyfuss JL, Bock A, Mackay M, Fischer JA: Intracolonic bioavailability of human calcitonin in man. Eur J Clin Pharmacol. 1992;43(5):527-31. [PubMed:1483490]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Alpha-n-acetylglucosaminidase activity
Specific Function
Involved in the degradation of heparan sulfate.
Gene Name
NAGLU
Uniprot ID
P54802
Uniprot Name
Alpha-N-acetylglucosaminidase
Molecular Weight
82264.92 Da
References
  1. Simmons RE, Hjelle JT, Mahoney C, Deftos LJ, Lisker W, Kato P, Rabkin R: Renal metabolism of calcitonin. Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600. doi: 10.1152/ajprenal.1988.254.4.F593. [PubMed:2833122]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogen...
Gene Name
ANPEP
Uniprot ID
P15144
Uniprot Name
Aminopeptidase N
Molecular Weight
109538.68 Da
References
  1. Simmons RE, Hjelle JT, Mahoney C, Deftos LJ, Lisker W, Kato P, Rabkin R: Renal metabolism of calcitonin. Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600. doi: 10.1152/ajprenal.1988.254.4.F593. [PubMed:2833122]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Phosphoglucomutase activity
Specific Function
This enzyme participates in both the breakdown and synthesis of glucose.
Gene Name
PGM1
Uniprot ID
P36871
Uniprot Name
Phosphoglucomutase-1
Molecular Weight
61448.575 Da
References
  1. Simmons RE, Hjelle JT, Mahoney C, Deftos LJ, Lisker W, Kato P, Rabkin R: Renal metabolism of calcitonin. Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600. doi: 10.1152/ajprenal.1988.254.4.F593. [PubMed:2833122]

Drug created on September 14, 2010 10:21 / Updated on August 02, 2019 07:55