DT-Web

DB00106 - Abarelix


Identification
Name Abarelix
Accession Number DB00106 (BIOD00051, BTD00051)
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1416.0630
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For palliative treatment of advanced prostate cancer.
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.
Protein binding 96-99%
Biotransformation 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
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
Interactions
Drug Interactions
Drug Mechanism of 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


Gonadotropin-releasing hormone receptor
Name Gonadotropin-releasing hormone receptor
Gene Name GNRHR
Pharmacological action yes
Actions antagonist
References
  • Debruyne FM: Gonadotropin-releasing hormone antagonist in the management of prostate cancer. Rev Urol. 2004;6 Suppl 7:S25-32. - Pubmed
DTHybrid score 1.3256

Predictions


Id Partner name Gene Name Score
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.2629
3811 Cytochrome P450 19A1 CYP19A1 0.0487
1649 Small inducible cytokine A2 CCL2 0.0242
756 Sex hormone-binding globulin SHBG 0.017
614 Progesterone receptor PGR 0.0157
146 Androgen receptor AR 0.0135
136 Estrogen receptor ESR1 0.0125
4512 Cytochrome P450 3A4 CYP3A4 0.0079
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