DrugBank: Abarelix (DB00106)

targets (1)

Identification

Name

Abarelix

Accession Number

DB00106 (BIOD00051, BTD00051)

Type

biotech

Groups

approved, withdrawn

Description

Synthetic decapeptide antagonist to gonadotropin releasing hormone (GnRH). It is marketed by Praecis Pharmaceuticals as Plenaxis. Praecis announced in June 2006 that it was voluntarily withdrawing the drug from the market.

Protein structure

Protein chemical formula

C₇₂H₉₅ClN₁₄O₁₄

Protein average weight

1416.0630

Sequences

Synonyms

Not Available

Salts

Not Available

Brand names

Name	Company
Plenaxis	Praecis Pharmaceuticals

Brand mixtures

Not Available

Categories

Antineoplastic Agents
Anti-Testosterone Agents

CAS number

183552-38-7

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For palliative treatment of advanced prostate cancer.

Pharmacodynamics

Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis.

Mechanism of action

Abarelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion.

Absorption

Following IM administration of 100 mg, abarelix is absorbed slowly with a mean peak concentration of 43.4 ng/mL observed approximately 3 days after the injection.

Volume of distribution

Not Available

Protein binding

96-99%

Metabolism

In vitro hepatocyte (rat, monkey, human) studies and in vivo studies in rats and monkeys showed that the major metabolites of abarelix were formed via hydrolysis of peptide bonds. No significant oxidative or conjugated metabolites of abarelix were found either in vitro or in vivo. There is no evidence of cytochrome P-450 involvement in the metabolism of abarelix.

Route of elimination

Not Available

Half life

13.2 ± 3.2 days

Clearance

Not Available

Toxicity

The maximum tolerated dose of abarelix has not been determined. The maximum dose used in clinical studies was 150 mg. There have been no reports of accidental overdose with abarelix.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Speciality european pharma ltd

Packagers

Dosage forms

Form	Route	Strength
Injection, powder, for suspension	Intramuscular

Prices

Not Available

Patents

Country	Patent Number	Approved	Expires (estimated)
United States	5968895	1996-12-11	2016-12-11
United States	6423686	1995-06-07	2015-06-07

Properties

State

liquid

Experimental Properties

Not Available

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PharmGKB	PA164754915
IUPHAR	1188
Guide to Pharmacology	1188
RxList	http://www.rxlist.com/cgi/generic/plenaxis.htm
Drugs.com	http://www.drugs.com/cdi/abarelix.html
Wikipedia	http://en.wikipedia.org/wiki/Abarelix

ATC Codes

L02BX01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

show (121 KB)

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Food Interactions

Not Available

Targets
1. Gonadotropin-releasing hormone receptor Pharmacological action: yes Actions: antagonist Receptor for gonadotropin releasing hormone (GnRH) that mediate the action of GnRH to stimulate the secretion of the gonadotropic hormones (LH and FSH). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act a an inhibitor of GnRH-R signaling Organism class: human UniProt ID: P30968 Gene: GNRHR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Debruyne FM: Gonadotropin-releasing hormone antagonist in the management of prostate cancer. Rev Urol. 2004;6 Suppl 7:S25-32. Pubmed

Targets

1. Gonadotropin-releasing hormone receptor

Pharmacological action: yes
Actions: antagonist

Receptor for gonadotropin releasing hormone (GnRH) that mediate the action of GnRH to stimulate the secretion of the gonadotropic hormones (LH and FSH). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act a an inhibitor of GnRH-R signaling

Organism class: human
UniProt ID: P30968 Link_out

Gene: GNRHR Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Debruyne FM: Gonadotropin-releasing hormone antagonist in the management of prostate cancer. Rev Urol. 2004;6 Suppl 7:S25-32. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on January 13, 2011 11:40