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
Db05829
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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
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
Medicalerrors
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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.
DrugInteraction
AcalabrutinibThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Acalabrutinib.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Parathyroid hormone.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Parathyroid hormone.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Acetyldigitoxin.
AfatinibThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Afatinib.
AldesleukinThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Aldesleukin.
AlectinibThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alectinib.
Alendronic acidThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alendronic acid.
Aminosalicylic acidThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Aminosalicylic acid.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Parathyroid hormone.
Interactions
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Food Interactions
No interactions found.

Products

Products
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International/Other Brands
Preos (NPS Pharmaceuticals, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NatparInjection, powder, for solution25 ?gSubcutaneousShire2020-12-16Not applicableEU flag
NatparInjection, powder, for solution75 ?gSubcutaneousShire2020-12-16Not applicableEU flag
NatparInjection, powder, for solution100 ?gSubcutaneousShire2020-12-16Not applicableEU flag
NatparInjection, powder, for solution50 ?gSubcutaneousShire2020-12-16Not applicableEU flag
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution75 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUS flag
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution50 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUS flag
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution100 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUS flag
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution25 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUS flag
PreotactInjection, powder, for solution100 µgSubcutaneousNps Pharma Holdings Limited2016-09-232014-07-02EU flag

Categories

ATC Codes
H05AA03 — Parathyroid hormone
Drug Categories
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
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
  1. Sosa Henriquez M, Diez Perez A: [Parathyroid hormone in the treatment of osteoporosis]. An Med Interna. 2007 Feb;24(2):87-97. [Article]
UniProt
P01270
KEGG Compound
C16051
PubChem Substance
347910255
RxNav
1427222
Wikipedia
Preotact

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentChronic Hypoparathyroidism / Hypoparathyroidism1
4CompletedTreatmentOsteoporosis1
4CompletedTreatmentPostmenopausal Women With Primary Osteoporosis1
4RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19) / Hypoparathyroidism1
4TerminatedTreatmentBack pain1
4Unknown StatusTreatmentShoulder Fractures1
3Active Not RecruitingDiagnosticHypoparathyroidism1
3Active Not RecruitingTreatmentHypoparathyroidism1
3CompletedPreventionDisruption or Dehiscence of Closure of Sternum or Sternotomy1
3CompletedTreatmentHypoparathyroidism4

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous
Injection, powder, for solutionSubcutaneous100 ?g
Injection, powder, for solutionSubcutaneous25 ?g
Injection, powder, for solutionSubcutaneous50 ?g
Injection, powder, for solutionSubcutaneous75 ?g
Injection, powder, lyophilized, for solutionSubcutaneous100 ug/0.08mL
Injection, powder, lyophilized, for solutionSubcutaneous25 ug/0.08mL
Injection, powder, lyophilized, for solutionSubcutaneous50 ug/0.08mL
Injection, powder, lyophilized, for solutionSubcutaneous75 ug/0.08mL
Injection, powder, for solutionSubcutaneous100 µg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets
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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
  1. 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]
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
  1. 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