Buserelin

Identification

Summary

Buserelin is a LHRH agonist used for the palliative treatment of hormone-dependent advanced carcinoma of the prostate gland in males and treatment of endometriosis in females.

Brand Names
Suprefact
Generic Name
Buserelin
DrugBank Accession Number
DB06719
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 1239.447
Monoisotopic: 1238.656026893
Chemical Formula
C60H86N16O13
Synonyms
  • Buserelin
  • Buserelina
  • Busereline
  • Buserelinum
  • Etilamide
  • Tiloryth
External IDs
  • HOE 766
  • S 746766

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.

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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 AvailableHumans
AGonadotropin-releasing hormone receptorNot AvailableHumans
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

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
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.

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.
DrugInteraction
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Buserelin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Buserelin.
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.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Buserelin.
AlbiglutideThe therapeutic efficacy of Albiglutide can be decreased when used in combination with Buserelin.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Buserelin.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Buserelin.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Buserelin.
AmantadineThe risk or severity of QTc prolongation can be increased when Amantadine is combined with Buserelin.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Buserelin acetate13U86G7YSP68630-75-1PYMDEDHDQYLBRT-DRIHCAFSSA-N
International/Other Brands
Cinnafact (Cinnagen)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SuprefactSolution1 mg / mLSubcutaneousCheplapharm Arzneimittel Gmbh1998-05-05Not applicableCanada flag
SuprefactSolution100 mcg / actNasalCheplapharm Arzneimittel Gmbh1998-02-03Not applicableCanada flag
Suprefact Depot 2 MonthsImplant6.3 mgSubcutaneousCheplapharm Arzneimittel Gmbh1997-02-10Not applicableCanada flag
Suprefact Depot 3 MonthsImplant9.45 mgSubcutaneousCheplapharm Arzneimittel Gmbh2000-02-24Not applicableCanada flag
Suprefact Inj 1mg/mlLiquid1 mg / mLSubcutaneousHoechst Canada Inc.1988-12-311998-08-25Canada flag
Suprefact Intranasal Solution 1mg/mlSpray1 mg / mLNasalHoechst Canada Inc.1988-12-311996-08-29Canada flag
Suprefact Liq 1mg/mlLiquid1 mg / mLNasalHoechst Roussel Canada Inc.1993-12-312000-07-28Canada flag

Categories

ATC Codes
L02AE01 — Buserelin
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
PXW8U3YXDV
CAS number
57982-77-1
InChI Key
CUWODFFVMXJOKD-UVLQAERKSA-N
InChI
InChI=1S/C60H86N16O13/c1-7-64-57(87)48-15-11-23-76(48)58(88)41(14-10-22-65-59(61)62)69-51(81)42(24-33(2)3)70-56(86)47(31-89-60(4,5)6)75-52(82)43(25-34-16-18-37(78)19-17-34)71-55(85)46(30-77)74-53(83)44(26-35-28-66-39-13-9-8-12-38(35)39)72-54(84)45(27-36-29-63-32-67-36)73-50(80)40-20-21-49(79)68-40/h8-9,12-13,16-19,28-29,32-33,40-48,66,77-78H,7,10-11,14-15,20-27,30-31H2,1-6H3,(H,63,67)(H,64,87)(H,68,79)(H,69,81)(H,70,86)(H,71,85)(H,72,84)(H,73,80)(H,74,83)(H,75,82)(H4,61,62,65)/t40-,41-,42-,43-,44-,45-,46-,47+,48-/m0/s1
IUPAC Name
(2S)-1-[(2S)-2-[(2S)-2-[(2R)-3-(tert-butoxy)-2-[(2S)-2-[(2S)-3-hydroxy-2-[(2S)-2-[(2S)-3-(1H-imidazol-5-yl)-2-{[(2S)-5-oxopyrrolidin-2-yl]formamido}propanamido]-3-(1H-indol-3-yl)propanamido]propanamido]-3-(4-hydroxyphenyl)propanamido]propanamido]-4-methylpentanamido]-5-carbamimidamidopentanoyl]-N-ethylpyrrolidine-2-carboxamide
SMILES
CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1

References

General References
  1. Link [Link]
KEGG Drug
D01831
PubChem Substance
347910362
ChemSpider
45545
RxNav
1825
ChEBI
135907
ChEMBL
CHEMBL2110824
Wikipedia
Buserelin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentFertility / Optimal Stimulation Protocol / Reproductive Endocrinology1
4CompletedTreatmentInfertility1
4CompletedTreatmentOHSS (Ovarian Hyperstimulation)1
4CompletedTreatmentOvarian Stimulation1
4CompletedTreatmentPregnant State1
4TerminatedTreatmentIn Vitro Fertilization (IVF) / Ovarian Stimulation1
4Unknown StatusTreatmentInfertility1
3Active Not RecruitingTreatmentProstate Cancer3
3CompletedTreatmentProstate Cancer2
3Not Yet RecruitingTreatmentAdenocarcinoma, Prostate1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SprayNasal
ImplantParenteral6.3 MG
ImplantParenteral9.45 MG
Injection, solution1 MG/ML
SolutionNasal100 mcg / act
SolutionSubcutaneous1 mg / mL
SprayNasal0.1 MG
InjectionParenteral
Implant; injectionSubcutaneous
ImplantSubcutaneous6.3 mg
ImplantSubcutaneous9.45 mg
LiquidSubcutaneous1 mg / mL
InjectionSubcutaneous1 mg/ml
SprayNasal1 mg / mL
LiquidNasal1 mg / mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP-3.3ChemAxon
pKa (Strongest Acidic)9.49ChemAxon
pKa (Strongest Basic)11.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area438.27 Å2ChemAxon
Rotatable Bond Count33ChemAxon
Refractivity334.23 m3·mol-1ChemAxon
Polarizability131.48 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. Maeda K, Kitawaki J, Yokota K, Noguchi T, Urabe M, Yamamoto T, Honjo H: [Effects of gonadotropin-releasing hormone and its analogue (buserelin) on aromatase in cultured human granulosa cells]. Nihon Sanka Fujinka Gakkai Zasshi. 1996 Feb;48(2):89-95. [Article]

Drug created on June 07, 2010 22:44 / Updated on October 16, 2021 12:31