Identification

Name
Buserelin
Accession Number
DB06719
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Description

Buserelin is a synthetic peptide analog of the luteinizing hormone-releasing hormone (LHRH) agonist, which stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). It is used in prostate cancer treatment.

Protein structure
Db06719
Protein chemical formula
C62H90N16O15
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • (Des-Gly10,D-Ser(tBu)6,Pro-NHEt9)-LHRH
  • Buserelina
  • D-Ser(Tbu)6EA10LHRH
  • Etilamide
  • Tiloryth
Product Ingredients
IngredientUNIICASInChI Key
Buserelin acetate13U86G7YSP68630-75-1PYMDEDHDQYLBRT-DRIHCAFSSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SuprefactSolution1 mgNasalSanofi Aventis1998-02-03Not applicableCanada
SuprefactSolution1 mgSubcutaneousSanofi Aventis1998-05-05Not applicableCanada
Suprefact Depot 2 MonthsImplant6.3 mgSubcutaneousSanofi Aventis1997-02-10Not applicableCanada
Suprefact Depot 3 MonthsImplant9.45 mgSubcutaneousSanofi Aventis2000-02-24Not applicableCanada
Suprefact Inj 1mg/mlLiquid1 mgSubcutaneousHoechst Canada Inc.1988-12-311998-08-25Canada
Suprefact Intranasal Solution 1mg/mlSpray1 mgNasalHoechst Canada Inc.1988-12-311996-08-29Canada
Suprefact Liq 1mg/mlLiquid1 mgNasalHoechst Roussel Canada Inc.1993-12-312000-07-28Canada
International/Other Brands
Cinnafact (Cinnagen)
Categories
UNII
PXW8U3YXDV
CAS number
57982-77-1

Pharmacology

Indication

Buserelin may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), and in assisted reproduction.

Associated Conditions
Pharmacodynamics

The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours. Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50-500 mcg SC/day or 300-1200 mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.

Mechanism of action

Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones.

TargetActionsOrganism
ALutropin-choriogonadotropic hormone receptorNot AvailableHuman
AGonadotropin-releasing hormone receptorNot AvailableHuman
Absorption

Buserelin is water soluble and readily absorbed after subcutaneous injection (70% bioavailable). However, bioavailability after oral absorption. When administered correctly via the nasal route, it may be absorbed in the nasal mucosa to achieve sufficient plasma levels.

Volume of distribution

Buserelin circulates in serum predominantly in intact active form. Preferred accumulation is preferentially in the liver and kidneys as well as in the anterior pituitary lobe, the biological target organ.

Protein binding

15%

Metabolism

It is metabolized and subsequently inactivated by peptidase (pyroglutamyl peptidase and chymotrypsin-like endopeptidase) in the liver and kidneys as well as in the gastrointestinal tract. In the pituitary gland, it is inactivated by membrane-located enzymes.

Route of elimination

Buserelin and its inactive metabolites are excreted via the renal and biliary routes. In man it is excreted in urine at 50% in its intact form.

Half life

The elimination half-life is approximately 50 to 80 minutes following intravenous administration, 80 minutes after subcutaneous administration and approximately 1 to 2 hours after intranasal administration.

Clearance
Not Available
Toxicity

Buserelin may induce early, transient increase in serum testosterone or estradiol which can lead in the exacerbation of signs and symptoms of metastatic prostate cancer or endometriosis. Adverse reactions reported at more than 10% occurrence include headache, loss of libido in patients with prostate cancer, hot flashes, hypermenorrhea, decreased libido in prostate cancer and endometriosis, flatulence, impotence, vaginal dryness, back pain and nasal mucosa irritation.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Buserelin.
AbexinostatThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Abexinostat.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Buserelin.
AcebutololThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Acebutolol.
AceprometazineThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Aceprometazine.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Buserelin.
AcetyldigoxinThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Acetyldigoxin.
AcrivastineThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Buserelin is combined with Adenosine.
AICA ribonucleotideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Buserelin.
Food Interactions
Not Available

References

General References
  1. Link [Link]
External Links
KEGG Drug
D01831
PubChem Substance
347910362
ChEMBL
CHEMBL1909304
Wikipedia
Buserelin
ATC Codes
L02AE01 — Buserelin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
  • 92:00.00 — Miscellaneous Therapeutic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentProstate Cancer1
1TerminatedTreatmentNon Castrate Metastatic Prostate Cancer1
1, 2CompletedTreatmentOvarian Stimulation1
1, 2Unknown StatusTreatmentAssisted Reproductive Technology therapy1
3Active Not RecruitingTreatmentProstate Cancer3
3CompletedTreatmentProstate Cancer2
3SuspendedTreatmentInfertilities1
3TerminatedTreatmentProstate Cancer1
3Unknown StatusScreeningEmbryo's Genetic and Chromosomal Quality1
3Unknown StatusTreatmentInfertilities1
4CompletedTreatmentInfertilities1
4CompletedTreatmentOHSS (Ovarian Hyperstimulation)1
4CompletedTreatmentOvarian Stimulation1
4CompletedTreatmentPregnancy1
4RecruitingTreatmentInfertilities1
4TerminatedTreatmentAssisted Reproductive Technology therapy / Ovarian Stimulation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionNasal1 mg
SolutionSubcutaneous1 mg
ImplantSubcutaneous6.3 mg
ImplantSubcutaneous9.45 mg
LiquidSubcutaneous1 mg
SprayNasal1 mg
LiquidNasal1 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Luteinizing hormone receptor activity
Specific Function
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name
LHCGR
Uniprot ID
P22888
Uniprot Name
Lutropin-choriogonadotropic hormone receptor
Molecular Weight
78642.01 Da
References
  1. Kirby RS, Fitzpatrick JM, Clarke N: Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4. doi: 10.1111/j.1464-410X.2009.08924.x. [PubMed:20053189]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Peptide binding
Specific Function
Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone...
Gene Name
GNRHR
Uniprot ID
P30968
Uniprot Name
Gonadotropin-releasing hormone receptor
Molecular Weight
37730.355 Da
References
  1. Kirby RS, Fitzpatrick JM, Clarke N: Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4. doi: 10.1111/j.1464-410X.2009.08924.x. [PubMed:20053189]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 07, 2010 16:44 / Updated on December 18, 2018 05:46