Parathyroid Hormone - Drugbank

Home , Cymarin, Gitoformate, Lanatoside C

6/20/2018 Parathyroid hormone - DrugBank

Parathyroid hormone

Targets (2) Biointeractions (2)

IDENTIFICATION

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. 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 structure

https://www.drugbank.ca/drugs/DB05829 1/11 6/20/2018 Parathyroid hormone - DrugBank

Protein chemical formula

C408H674N126O126S2

Protein average weight 9420.0 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 IDs

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

Prescription Products

MARKETING MARKETING NAME ↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER ↑↓ START ↑↓ END ↑↓ ↑↓ ↑↓

NATPARA Injection 25 ug/ 08mL Subcutaneous Shire Nps 2015-01-23 Not applicable https://www.drugbank.ca/drugs/DB05829 2/11 6/20/2018 Parathyroid hormone - DrugBank NATPARA Injection, 25 ug/.08mL Subcutaneous Shire Nps 2015 01 23 Not applicable (parathyroid powder, Pharmaceuticals, hormone) lyophilized, Inc. for solution

NATPARA Injection, 75 ug/.08mL Subcutaneous Shire Nps 2015-01-23 Not applicable (parathyroid powder, Pharmaceuticals, hormone) lyophilized, Inc. for solution

NATPARA Injection, 50 ug/.08mL Subcutaneous Shire Nps 2015-01-23 Not applicable (parathyroid powder, Pharmaceuticals, hormone) lyophilized, Inc. for solution

NATPARA Injection, 100 ug/.08mL Subcutaneous Shire Nps 2015-01-23 Not applicable (parathyroid powder, Pharmaceuticals, hormone) lyophilized, Inc. for solution

Showing 1 to 4 of 4 entries ‹ ›

Unapproved/Other Products

MARKETING MARKETING NAME ↑↓ INGREDIENTS DOSAGE ↑↓ ROUTE ↑↓ LABELLER ↑↓ START ↑↓ END ↑↓ ↑↓ ↑↓

Preotact Parathyroid Injection, Subcutaneous Nps Pharma 2006-04-24 2014-07-11 hormone (100 powder, for Holdings µg) solution Limited

Showing 1 to 1 of 1 entries ‹ ›

International/Other Brands

Preos (NPS Pharmaceuticals, Inc.)

Categories

Amino Acids, Peptides, and Proteins

Calcium Homeostasis

Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists

Parathyroid Hormone

Parathyroid Hormones and Analogues

Peptide Hormones

Peptides

Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins https://www.drugbank.ca/drugs/DB05829 3/11 6/20/2018 Parathyroid hormone - DrugBank

UNII N19A0T0E5J

CAS number 9002-64-6

PHARMACOLOGY

Indication For use/treatment in osteoporosis.

Associated Conditions

Hypocalcemia

Parathyroid deﬁciency

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.

U Parathyroid hormone/parathyroid hormone-related peptide receptor

activator

Human

A Parathyroid hormone 2 receptor

activator

Human

Absorption The absolute bioavailability of 100 micrograms of Preotact aer subcutaneous administration in the abdomen is 55%. https://www.drugbank.ca/drugs/DB05829 4/11 6/20/2018 Parathyroid hormone - DrugBank

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

Protein binding Not 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 elimination Not 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 life The 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.

Toxicity Not Available

Aﬀected organisms

Humans and other mammals

Pathways Not Available

Pharmacogenomic Eﬀects/ADRs

Not Available

https://www.drugbank.ca/drugs/DB05829 5/11 6/20/2018 Parathyroid hormone - DrugBank

INTERACTIONS

Drug Interactions

DRUG ↑↓ INTERACTION ↑↓ DRUG GROUP ↑↓ Acetyldigitoxin The risk or severity of adverse eﬀects can be increased when Parathyroid Approved hormone is combined with Acetyldigitoxin.

Acetyldigoxin The risk or severity of adverse eﬀects can be increased when Parathyroid Experimental hormone is combined with Acetyldigoxin.

Alendronic acid The therapeutic eﬃcacy of Parathyroid hormone can be decreased when Approved used in combination with Alendronic acid.

Cymarin The risk or severity of adverse eﬀects can be increased when Parathyroid Experimental hormone is combined with Cymarin.

Deslanoside The risk or severity of adverse eﬀects can be increased when Parathyroid Approved hormone is combined with Deslanoside.

Digitoxin The risk or severity of adverse eﬀects can be increased when Parathyroid Approved, hormone is combined with Digitoxin. Investigational

Digoxin The risk or severity of adverse eﬀects can be increased when Parathyroid Approved hormone is combined with Digoxin.

Digoxin Immune The risk or severity of adverse eﬀects can be increased when Parathyroid Approved Fab (Ovine) hormone is combined with Digoxin Immune Fab (Ovine).

Gitoformate The risk or severity of adverse eﬀects can be increased when Parathyroid Experimental hormone is combined with Gitoformate.

Lanatoside C The risk or severity of adverse eﬀects can be increased when Parathyroid Experimental hormone is combined with Lanatoside C.

Showing 1 to 10 of 15 entries ‹ ›

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 https://www.drugbank.ca/drugs/DB05829 6/11 6/20/2018 Parathyroid hormone - DrugBank

UniProt P01270

KEGG Compound C16051

PubChem Substance 347910255

Wikipedia Preotact

ATC Codes H05AA03 — Parathyroid hormone H05AA — Parathyroid hormones and analogues H05A — PARATHYROID HORMONES AND ANALOGUES H05 — CALCIUM HOMEOSTASIS H — SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS

CLINICAL TRIALS

Clinical Trials

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓ 0 Completed Not Available Bone destruction / Bone Diseases, Endocrine / 1 Hyperparathyroidism

1 Completed Treatment Postmenopausal Osteoporosis (PMO) 1

1 Completed Treatment Bone destruction 1

1 Completed Treatment Parathyroid deﬁciency 1

1 Recruiting Treatment Parathyroid deﬁciency 1

1 Terminated Treatment Osteopetrosis 1

1 Withdrawn Not Available Bone destruction / Bone Diseases, Endocrine / 1 Hypercalcemia of Malignancy / Hyperparathyroidism

2 Completed Treatment Postmenopausal Osteoporosis (PMO) 1

2 Completed Treatment Bone destruction 7

2 Completed Treatment Parathyroid deﬁciency 1

Showing 1 to 10 of 32 entries ‹ ›

PHARMACOECONOMICS

Manufacturers

Not Available https://www.drugbank.ca/drugs/DB05829 7/11 6/20/2018 Parathyroid hormone - DrugBank

Packagers

Not Available

Dosage forms

FORM ↑↓ ROUTE ↑↓ STRENGTH ↑↓ Injection, powder, lyophilized, for solution Subcutaneous 100 ug/.08mL

Injection, powder, lyophilized, for solution Subcutaneous 25 ug/.08mL

Injection, powder, lyophilized, for solution Subcutaneous 50 ug/.08mL

Injection, powder, lyophilized, for solution Subcutaneous 75 ug/.08mL

Injection, powder, for solution Subcutaneous 100 µg

Showing 1 to 5 of 5 entries ‹ ›

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 https://www.drugbank.ca/drugs/DB05829 8/11 6/20/2018 Parathyroid hormone - DrugBank

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

1. Parathyroid hormone/parathyroid hormone-related peptide receptor

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 phosphatid...

Gene Name PTH1R

Uniprot ID

Q03431 https://www.drugbank.ca/drugs/DB05829 9/11 6/20/2018 Parathyroid hormone - DrugBank

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]

2. Parathyroid hormone 2 receptor

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...

Gene Name PTH2R

Uniprot ID P49190

Uniprot Name Parathyroid hormone 2 receptor

Molecular Weight 62235.335 Da

References

https://www.drugbank.ca/drugs/DB05829 10/11 6/20/2018 Parathyroid hormone - DrugBank

Drug created on November 18, 2007 11:28 / Updated on June 02, 2018 07:40

About About DrugBank DrugBank Blog Wishart Research Group Terms of Use Privacy Policy

Support FAQ Help Email Support

Commercial Products API Pricing API Docs Data Licenses Support

This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-proﬁt organization that is leading Canada's national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc.

https://www.drugbank.ca/drugs/DB05829 11/11