Parathyroid hormone

Identification

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Name
Parathyroid hormone
Accession Number
DB05829
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Description

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).

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution50 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution25 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution100 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
NATPARA (parathyroid hormone)Injection, powder, lyophilized, for solution75 ug/0.08mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
PreotactInjection, powder, for solution100 µgSubcutaneousNps Pharma Holdings Limited2006-04-242014-07-11Eu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Preos (NPS Pharmaceuticals, Inc.)
Categories
UNII
N19A0T0E5J
CAS number
9002-64-6

Pharmacology

Indication

For use/treatment in osteoporosis.

Associated Conditions
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
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Parathyroid hormone.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Parathyroid hormone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Parathyroid hormone.
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.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Acetyldigitoxin.
AcetyldigoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Acetyldigoxin.
AfatinibThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Afatinib.
AlaproclateThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alaproclate.
AldesleukinThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Aldesleukin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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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

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. [PubMed:17590097]
External Links
UniProt
P01270
KEGG Compound
C16051
PubChem Substance
347910255
Wikipedia
Preotact
ATC Codes
H05AA03 — Parathyroid hormone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedNot AvailableBone Diseases, Endocrine / Hyperparathyroidism / Osteoporosis1
1CompletedTreatmentOsteoporosis1
1CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
1CompletedTreatmentParathyroid deficiency2
1TerminatedTreatmentOsteopetrosis1
1WithdrawnNot AvailableBone Diseases, Endocrine / Hypercalcemia of Malignancy / Hyperparathyroidism / Osteoporosis1
2Active Not RecruitingTreatmentOsteogenesis Imperfecta1
2CompletedTreatmentOsteoporosis7
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
2CompletedTreatmentParathyroid deficiency2
2TerminatedPreventionAgnogenic Myeloid Metaplasia / Aplastic Anaemia (AA) / Chronic Lymphocytic Leukaemia (CLL) / Chronic Myeloid Leukemia (CML) / Hodgkins Disease (HD) / Leukemia, Lymphocytic, Acute / Leukemia, Myelocytic, Acute / Malignant Lymphomas1
2TerminatedTreatmentHypocalcemia1
2WithdrawnTreatmentShoulder Fractures / Trochanteric Fractures1
2, 3CompletedTreatmentOsteoporosis1
2, 3CompletedTreatmentParathyroid deficiency1
3Active Not RecruitingDiagnosticParathyroid deficiency1
3Active Not RecruitingTreatmentParathyroid deficiency2
3CompletedPreventionDisruption or Dehiscence of Closure of Sternum or Sternotomy1
3CompletedTreatmentOsteoporosis6
3CompletedTreatmentParathyroid deficiency4
3Not Yet RecruitingTreatmentChronic Hypoparathyroidism1
3TerminatedTreatmentDiGeorge's syndrome / Parathyroid deficiency1
4Active Not RecruitingTreatmentChronic Hypoparathyroidism / Parathyroid deficiency1
4CompletedTreatmentOsteoporosis2
4CompletedTreatmentPostmenopausal Women With Primary Osteoporosis1
4RecruitingTreatmentParathyroid deficiency1
4TerminatedTreatmentBack Pain1
4Unknown StatusTreatmentShoulder Fractures1
Not AvailableActive Not RecruitingTreatmentOsteoporosis1
Not AvailableCompletedNot AvailableClinical Use of PTH(1-84)1
Not AvailableCompletedDiagnosticControlled / Healthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
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

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
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. [PubMed:10837469]
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. [PubMed:10837469]

Drug created on November 18, 2007 11:28 / Updated on August 02, 2019 07:47