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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Hypocalcemia •••••••••••• Management of Hypoparathyroidism •••••••••••• - 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 AParathyroid hormone 2 receptor activatorHumans UParathyroid hormone/parathyroid hormone-related peptide receptor activatorHumans - 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 Integrate drug-drug
interactions in your softwareAcalabrutinib 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. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Preos (NPS Pharmaceuticals, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Natpar Injection, powder, for solution 100 ?g Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2020-12-16 Not applicable EU Natpar Injection, powder, for solution 25 ?g Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2020-12-16 Not applicable EU Natpar Injection, powder, for solution 75 ?g Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2020-12-16 Not applicable EU Natpar Injection, powder, for solution 50 ?g Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2020-12-16 Not applicable EU NATPARA (parathyroid hormone) Injection, powder, lyophilized, for solution 50 ug/0.08mL Subcutaneous Takeda Pharmaceuticals America, Inc. 2015-01-23 Not applicable US
Categories
- ATC Codes
- H05AA03 — Parathyroid hormone
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Calcium Homeostasis
- Calcium-Regulating Hormones and Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Parathyroid Hormones and Analogues
- Peptide Hormones
- Peptides
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Thyroid Products
- 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
- 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
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Chronic Hypoparathyroidism / Hypoparathyroidism 1 4 Completed Treatment Coronavirus Disease 2019 (COVID‑19) / Hypoparathyroidism 1 4 Completed Treatment Osteoporosis 1 4 Completed Treatment Postmenopausal Women With Primary Osteoporosis 1 4 Terminated Treatment Back pain 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Subcutaneous 100 MCG Injection, powder, for solution Subcutaneous 100 ?g Injection, powder, for solution Subcutaneous 25 MCG Injection, powder, for solution Subcutaneous 25 ?g Injection, powder, for solution Subcutaneous 50 MCG Injection, powder, for solution Subcutaneous 50 ?g Injection, powder, for solution Subcutaneous 75 ?g Injection, powder, for solution Subcutaneous 75 MCG 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 Injection, powder, for solution Subcutaneous 100 µg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- 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]
- 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]
Drug created at November 18, 2007 18:28 / Updated at May 20, 2024 11:59