Human calcitonin

Identification

Generic Name

Human calcitonin

DrugBank Accession Number

DB06773

Background

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

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Hormones

Protein Structure

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

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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

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Contraindications & Blackbox Warnings

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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

Target	Actions	Organism
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 clearance 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

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Alendronic acid	The risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Alendronic acid.
Clodronic acid	The risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Clodronic acid.
Etidronic acid	The risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Etidronic acid.
Ibandronate	The risk or severity of hypocalcemia can be increased when Human calcitonin is combined with Ibandronate.
Lithium carbonate	Human calcitonin may increase the excretion rate of Lithium carbonate which could result in a lower serum level and potentially a reduction in efficacy.

Food Interactions

Not Available

Categories

ATC Codes

H05BA03 — Calcitonin (human synthetic)

• H05BA — Calcitonin preparations
• H05B — ANTI-PARATHYROID AGENTS
• H05 — CALCIUM HOMEOSTASIS
• H — SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS

Drug Categories

• Bone Density Conservation Agents
• Calcitonin Preparations
• Calcium Homeostasis
• Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins

Chemical TaxonomyProvided by Classyfire

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

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

I0IO929019

CAS number

21215-62-3

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. [Article]
2. Authors unspecified: Clinical applications of calcitonin. Can Med Assoc J. 1971 Aug 7;105(3):238-9. [Article]
3. Authors unspecified: Editorial: Paget's disease and calcitonin. Br Med J. 1975 Aug 30;3(5982):505-6. [Article]
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. [Article]
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. [Article]
6. Yamamoto Y, Noguchi T, Takahashi N: [Effects of calcitonin on osteoclast]. Clin Calcium. 2005 Mar;15(3):147-51. doi: CliCa0503467471. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

External Links

PubChem Substance

347910370

RxNav

235481

Wikipedia

Calcitonin

MSDS

Download (22.1 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	1 mg/ml	'MSDS'

Targets

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Details1. Alpha-actinin-1

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. [Article]

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Drug created at September 14, 2010 16:21 / Updated at December 15, 2023 23:52