Parathyroid hormone

Identification

Summary

Parathyroid hormone is an analog of human parathyroid hormone (PTH) used to treat hypocalcemia caused by hypoparathyroidism.

Brand Names

Natpara

Generic Name

Parathyroid hormone

DrugBank Accession Number

DB05829

Background

Parathyroid hormone (PTH) is a single-chain polypeptide composed of 84 amino acids. Available as Preotact, it is an identical form of human recombinant hormome which produced as a fusion protein undergoeing post-translational processing involving the cleavage of the OmpA leader sequence, leaving the mature protein as a single-chain 84 amino-acids polypeptide (9.4 kDa).

Preotact is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures and is marketed in Europe by Nycomed. Preos is a registered trade mark owned by NPS Pharmaceuticals, Inc. The name Preos and the New Drug Application is pending approval by the U.S. Food and Drug Administration (FDA).

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Hormones

Protein Structure

Protein Chemical Formula: C₄₀₈H₆₇₄N₁₂₆O₁₂₆S₂
Protein Average Weight: 9420.0 Da

Sequences

>Parathyroid hormone
SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNFVALGAPLAPRDAGSQRPRKKEDNVLV
ESHEKSLGEADKADVNVLTKAKSQ

Download FASTA Format

Synonyms

Parathormone
Parathormone (human recombinant)
Parathyrin
Parathyroid hormone
Parathyroid hormone (1-84) human recombinant
Parathyroid hormone (rDNA)
PTH
PTH(1-84)
rhPTH
rhPTH(1-84)
rPTH
rPTH(1-84)

External IDs

ALX-1-11
ALX-111
ALX1-11
NPSP-558
NPSP558

Pharmacology

Indication

For use/treatment in osteoporosis.

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Drug Discovery

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Parathyroid hormone is responsible for the fine regulation of serum calcium concentration on a minute-to-minute basis. This is achieved by the acute effects of the hormone on calcium resorption in bone and calcium reabsorption in the kidney. The phosphate mobilized from bone is excreted into the urine by means of the hormone's influence on renal phosphate handling. Parathyroid hormone also stimulates calcium absorption in the intestine, this being mediated indirectly by 1,25-dihydroxyvitamin D. Thus, a hypocalcemic stimulus of parathyroid hormone secretion results in an increased influx of calcium from three sources (bone, kidney, and intestine), resulting in a normalization of the serum calcium concentration without change in the serum phosphate concentration.

Mechanism of action

The biological actions of rhPTH are mediated through binding to at least two distinct high- affinity cell-surface receptors specific for the N-terminal and C-terminal regions of the molecule, both of which are required for normal bone metabolism. The N-terminal portion of the molecule is primarily responsible for the bone building effects of parathyroid hormone. The C-terminal portion of the molecule has antiresorptive activity and is necessary for normal regulation of N-terminal fragment activity.

Target	Actions	Organism
UParathyroid hormone/parathyroid hormone-related peptide receptor	activator	Humans
AParathyroid hormone 2 receptor	activator	Humans

Absorption

The absolute bioavailability after subcutaneous administration in the abdomen is 55% for doses of 100 micrograms.

Volume of distribution

The volume of distribution at steady-state following intravenous administration is approximately 5.4 liters with an interpatient variability of about 40%.

Protein binding

Not Available

Metabolism

PTH is primarily metabolised in the liver with lesser contributions by the kidney. Amino terminal fragments are metabolised in the liver while carboxyl terminal groups travel to the kidney for metabolism where they are also thought to have a role in regulation of PTH. Only about 30% of circulating hormone is present as the unfragmented form.

Route of elimination

Carboxy-terminal fragments are filtered by the kidney and subsequently broken down into even smaller fragments during tubular reuptake.

Half-life

1.5 hours.

Clearance

Not Available

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.

Drug	Interaction
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Acalabrutinib	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Acalabrutinib.
Acebutolol	The risk or severity of adverse effects can be increased when Acebutolol is combined with Parathyroid hormone.
Acetohexamide	The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Parathyroid hormone.
Acetyldigitoxin	The risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Acetyldigitoxin.
Afatinib	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Afatinib.
Aldesleukin	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Aldesleukin.
Alectinib	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alectinib.
Alendronic acid	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alendronic acid.
Aminosalicylic acid	The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Aminosalicylic acid.
Amphetamine	The risk or severity of adverse effects can be increased when Amphetamine is combined with Parathyroid hormone.

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Food Interactions

No interactions found.

Products

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International/Other Brands

Preos (NPS Pharmaceuticals, Inc.)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Natpar	Injection, powder, for solution	25 ?g	Subcutaneous	Shire	2020-12-16	Not applicable
Natpar	Injection, powder, for solution	75 ?g	Subcutaneous	Shire	2020-12-16	Not applicable
Natpar	Injection, powder, for solution	100 ?g	Subcutaneous	Shire	2020-12-16	Not applicable
Natpar	Injection, powder, for solution	50 ?g	Subcutaneous	Shire	2020-12-16	Not applicable
NATPARA (parathyroid hormone)	Injection, powder, lyophilized, for solution	75 ug/0.08mL	Subcutaneous	Shire-NPS Pharmaceuticals, Inc.	2015-01-23	Not applicable
NATPARA (parathyroid hormone)	Injection, powder, lyophilized, for solution	50 ug/0.08mL	Subcutaneous	Shire-NPS Pharmaceuticals, Inc.	2015-01-23	Not applicable
NATPARA (parathyroid hormone)	Injection, powder, lyophilized, for solution	100 ug/0.08mL	Subcutaneous	Shire-NPS Pharmaceuticals, Inc.	2015-01-23	Not applicable
NATPARA (parathyroid hormone)	Injection, powder, lyophilized, for solution	25 ug/0.08mL	Subcutaneous	Shire-NPS Pharmaceuticals, Inc.	2015-01-23	Not applicable
Preotact	Injection, powder, for solution	100 µg	Subcutaneous	Nps Pharma Holdings Limited	2016-09-23	2014-07-02

Chemical Identifiers

UNII: N19A0T0E5J
CAS number: 9002-64-6

References

Synthesis Reference

Robert L. Colescott, Geoffrey W. Tregear, "Synthesis of peptides with parathyroid hormone activity." U.S. Patent US4105602, issued May, 1977.

US4105602

General References

Sosa Henriquez M, Diez Perez A: [Parathyroid hormone in the treatment of osteoporosis]. An Med Interna. 2007 Feb;24(2):87-97. [Article]

External Links

UniProt: P01270
KEGG Compound: C16051
PubChem Substance: 347910255
RxNav: 1427222
Wikipedia: Preotact

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Chronic Hypoparathyroidism / Hypoparathyroidism	1
4	Completed	Treatment	Osteoporosis	1
4	Completed	Treatment	Postmenopausal Women With Primary Osteoporosis	1
4	Recruiting	Treatment	Coronavirus Disease 2019 (COVID‑19) / Hypoparathyroidism	1
4	Terminated	Treatment	Back pain	1
4	Unknown Status	Treatment	Shoulder Fractures	1
3	Active Not Recruiting	Diagnostic	Hypoparathyroidism	1
3	Active Not Recruiting	Treatment	Hypoparathyroidism	1
3	Completed	Prevention	Disruption or Dehiscence of Closure of Sternum or Sternotomy	1
3	Completed	Treatment	Hypoparathyroidism	4

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Subcutaneous
Injection, powder, for solution	Subcutaneous	100 ?g
Injection, powder, for solution	Subcutaneous	25 ?g
Injection, powder, for solution	Subcutaneous	50 ?g
Injection, powder, for solution	Subcutaneous	75 ?g
Injection, powder, lyophilized, for solution	Subcutaneous	100 ug/0.08mL
Injection, powder, lyophilized, for solution	Subcutaneous	25 ug/0.08mL
Injection, powder, lyophilized, for solution	Subcutaneous	50 ug/0.08mL
Injection, powder, lyophilized, for solution	Subcutaneous	75 ug/0.08mL
Injection, powder, for solution	Subcutaneous	100 µg

Prices

Not Available

Patents

Not Available

Properties

State: Solid
Experimental Properties: Not Available

Targets

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Details1. Parathyroid hormone/parathyroid hormone-related peptide receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Activator

General Function: Protein self-association
Specific Function: This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatid...
Gene Name: PTH1R
Uniprot ID: Q03431
Uniprot Name: Parathyroid hormone/parathyroid hormone-related peptide receptor
Molecular Weight: 66359.98 Da

References

Jin L, Briggs SL, Chandrasekhar S, Chirgadze NY, Clawson DK, Schevitz RW, Smiley DL, Tashjian AH, Zhang F: Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution. J Biol Chem. 2000 Sep 1;275(35):27238-44. [Article]

Details2. Parathyroid hormone 2 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Activator

General Function: Parathyroid hormone receptor activity
Specific Function: This is a specific receptor for parathyroid hormone. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. PTH2R may be responsible for PTH effects in a number of...
Gene Name: PTH2R
Uniprot ID: P49190
Uniprot Name: Parathyroid hormone 2 receptor
Molecular Weight: 62235.335 Da

References

Jin L, Briggs SL, Chandrasekhar S, Chirgadze NY, Clawson DK, Schevitz RW, Smiley DL, Tashjian AH, Zhang F: Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution. J Biol Chem. 2000 Sep 1;275(35):27238-44. [Article]

Drug created on November 18, 2007 18:28 / Updated on July 28, 2021 15:03

Parathyroid hormone

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

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References

References