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Identification
NameParathyroid hormone
Accession NumberDB05829
TypeBiotech
GroupsApproved, Investigational
DescriptionParathyroid hormone (PTH) is a single-chain polypeptide composed of 84 amino acids. As Preotact, it contains recombinant human parathyroid hormone which is identical to the full-length native 84-amino acid polypeptide. It is produced as a fusion protein. Post-translational processing involves the cleavage of the OmpA leader sequence, leaving the mature protein as a single-chain 84 amino-acids polypeptide (9.4 kDa) whose sequence is identical to that of the full-length native endogenous human PTH. It has no disulfide bonds and no glycosylation sites. Preotact is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures. Preotact 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 structureDb05829
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Protein chemical formulaC408H674N126O126S2
Protein average weight9420.0 Da
Sequences
>Parathyroid hormone
SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNFVALGAPLAPRDAGSQRPRKKEDNVLV
ESHEKSLGEADKADVNVLTKAKSQ
Download FASTA Format
Synonyms
hPTH
hPTH(1-84)
Parathormone
Parathormone (human recombinant)
Parathyrin
Parathyroid hormone
parathyroid hormone (1-84) human recombinant
parathyroid hormone (rDNA)
Preotact
PTH
PTH(1-84)
rhPTH
rhPTH(1-84)
rPTH
rPTH(1-84)
External Identifiers
  • ALX-111
  • ALX1-11
  • NPSP-558
  • NPSP558
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Natpara (parathyroid Hormone)injection, powder, lyophilized, for solution25 ug/.08mLsubcutaneousNPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
Natpara (parathyroid Hormone)injection, powder, lyophilized, for solution50 ug/.08mLsubcutaneousNPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
Natpara (parathyroid Hormone)injection, powder, lyophilized, for solution75 ug/.08mLsubcutaneousNPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
Natpara (parathyroid Hormone)injection, powder, lyophilized, for solution100 ug/.08mLsubcutaneousNPS Pharmaceuticals, Inc.2015-01-23Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PreosNPS Pharmaceuticals, Inc.
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIN19A0T0E5J
CAS number9002-64-6
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor use/treatment in osteoporosis.
PharmacodynamicsParathyroid 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 actionThe 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.
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AbsorptionThe absolute bioavailability of 100 micrograms of Preotact after subcutaneous administration in the abdomen is 55%.
Volume of distribution

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

Protein bindingNot Available
Metabolism

PTH is metabolised in the liver and to a lesser extent in the kidney. Parathyroid hormone is efficiently removed from the blood by a receptor-mediated process in the liver and is broken down into smaller peptide fragments. The fragments derived from the amino-terminus are further degraded within the cell while the fragments derived from the carboxy-terminus are released back into the blood and cleared by the kidney. These carboxy-terminal fragments are thought to play a role in the regulation of PTH activity. Under normal physiological conditions full-length PTH constitutes only 5-30% of the circulating forms of the molecule, while 70-95% is present as carboxy-terminal fragments. Following administration of Preotact, carboxy-terminal fragments make up about 60-90% of the circulating forms of the molecule. Intersubject variability in systemic clearance is about 15%.

Route of eliminationNot excreted from the body in its intact form. Circulating carboxy-terminal fragments are filtered by the kidney, but are subsequently broken down into even smaller fragments during tubular reuptake.
Half lifeThe mean half-life is approximately 1.5 hours.
Clearance

PTH is rapidly cleared from plasma, primarily by Kupffer cells in the liver. To a lesser extent, PTH is cleared by filtration and reabsorption by the kidney.

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionsubcutaneous100 ug/.08mL
Injection, powder, lyophilized, for solutionsubcutaneous25 ug/.08mL
Injection, powder, lyophilized, for solutionsubcutaneous50 ug/.08mL
Injection, powder, lyophilized, for solutionsubcutaneous75 ug/.08mL
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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
ATC CodesH05AA03
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Acetyldigitoxin.
Alendronic acidThe therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Alendronic acid.
DeslanosideThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Deslanoside.
DigitoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Digitoxin.
DigoxinThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Digoxin.
OuabainThe risk or severity of adverse effects can be increased when Parathyroid hormone is combined with Ouabain.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 phosphatidylinositol-calcium second messenger system.
Gene Name:
PTH1R
Uniprot ID:
Q03431
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
Human
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 physiological systems. It may play a significant role in pancreatic function. PTH2R presence in neurons indicates that it may function as a neurotransmitter receptor (By similarity).
Gene Name:
PTH2R
Uniprot ID:
P49190
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 ]
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Drug created on November 18, 2007 11:28 / Updated on September 26, 2016 12:53