Triptorelin

Identification

Summary

Triptorelin is a GnRH agonist indicated for the palliative treatment of advanced prostate cancer.

Brand Names
Decapeptyl, Trelstar, Triptodur
Generic Name
Triptorelin
DrugBank Accession Number
DB06825
Background

Triptorelin is a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion. After chronic, continuous administration, this agent effects sustained decreases in LH and FSH production and testicular and ovarian steroidogenesis. Serum testosterone concentrations may fall to levels typically observed in surgically castrated men.

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 1311.473
Monoisotopic: 1310.630874772
Chemical Formula
C64H82N18O13
Synonyms
  • (6-D-Tryptophan)luteinizing hormone-releasing hormone
  • (D-Trp6)-GnRH
  • Luteinizing hormone-releasing factor (pig), 6-D-tryptophan
  • pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2
  • Triptorelin
  • Triptorelina
  • Triptoreline
  • Triptorelinum
External IDs
  • AY-25650
  • CL 118,532
  • CL-118532
  • WY-42462

Pharmacology

Indication

Triptorelin is indicated for the palliative treatment of advanced prostate cancer.

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
Associated Therapies
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 first administration of triptorelin is followed by a transient surge of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol,and testosterone. The time, peak and decline of testosterone in the body varies depending on the dose administered. This initial surge is often responsible for worsening of prostate cancer symptoms such as urethral or bladder outlet obstruction, bone pain, spinal cord injury and hematuria in the early stages. A sustained decrease in FSH and LH, and significant reduction of testicular steroidogenesis is usually seen 2-4 weeks post-initiation of therapy. This result is a reduction of serum testosterone to levels which are typically seen in surgically castrated men. Ultimately, tissues and functions that require these hormones become inactive. The effects of triptorelin can usually be reversed once the drug is discontinued.

Mechanism of action

Triptorelin is a synthetic agonist analog of gonadotropin releasing hormone (GnRH). Animal studies comparing triptorelin to native GnRH found that triptorelin had 13 fold higher releasing activity for luteinizing hormone, and 21-fold higher releasing activity for follicle-stimulating hormone.

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
agonist
Humans
Absorption

Following IV administration of triptorelin, triptorelin is completely absorbed.

Volume of distribution

After a single IV dose of 0.5mg, the volume of distribution of triptorelin peptide in healthy males was 30 - 33L.

Protein binding

Triptorelin does not bind to plasma proteins at clinically relevant concentrations.

Metabolism

The metabolism of triptorelin in humans is not well understood; however, metabolism likely does not involve hepatic enzymes such as cytochrome P450. Whether or not triptorelin affects, or how it affects other metabolizing enzymes is also poorly understood. Triptorelin has no identified metabolites.

Route of elimination

Elimination of triptorelin involves both the kidneys and the liver.

Half-life

The pharmacokinetics of triptorelin follows a 3 compartment model. The half lives are estimated to be 6 minutes, 45 minutes, and 3 hours respectively.

Clearance

In healthy male volunteers, total clearance of triptorelin was 211.9 mL/min.

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

Some of the most commonly reported adverse effects of triptorelin are hot flushes reported in 58.6% of patients, skeletal pain in 12.1%, impotence in 7.1%, and headache in 5.0%. Other reported adverse effects include injection site pain, general body pain, leg pain, fatigue, hypertension, dizziness, diarrhea, vomiting, insomnia, emotional lability, anemia, pruritus, urinary tract infections, and urinary retention. Triptorelin is classified as Pregnancy Category X and contraindicated in pregnant women or in women who may become pregnant. Hormonal changes caused by triptorelin increase the risk for pregnancy loss. Studies done on pregnant rats demonstrated maternal toxicity and embryo-fetal toxicities.

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 Triptorelin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Triptorelin.
AcrivastineThe risk or severity of QTc prolongation can be increased when Triptorelin is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Triptorelin is combined with Adenosine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Triptorelin.
AlbiglutideThe therapeutic efficacy of Albiglutide can be decreased when used in combination with Triptorelin.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Triptorelin.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Triptorelin.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Triptorelin.
AmantadineThe risk or severity of QTc prolongation can be increased when Amantadine is combined with Triptorelin.
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
Triptorelin acetate43OFW291R9140194-24-7HPPONSCISKROOD-OYLNGHKZSA-N
Triptorelin pamoate08AN7WA2G0124508-66-3ZBVJFYPGLGEMIN-OYLNGHKZSA-N
International/Other Brands
Diphereline (Ferring Pharmaceuticals) / Gonapeptyl (Ferring Pharmaceuticals) / Variopeptyl (Varian Darou Pajooh)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DecapeptylSolution0.1 mg / mLSubcutaneousFerring Pharmaceuticals2012-08-09Not applicableCanada flag
Trelstar11.25 mg/2mLIntramuscularVerity Pharmaceuticals Inc.2001-06-29Not applicableUS flag
TrelstarKit3.75 mg/2mLIntramuscularActavis Pharma Company2000-06-152018-10-31US flag
TrelstarInjection, powder, for suspension, extended release11.25 mg / vialIntramuscularKnight Therapeutics Inc.2005-12-15Not applicableCanada flag
TrelstarInjection, powder, lyophilized, for suspension3.75 mg/2mLIntramuscularActavis Pharma Company2000-06-152018-10-31US flag
Trelstar11.25 mg/2mLIntramuscularAllergan, Inc.2001-06-29Not applicableUS flag
TrelstarKit22.5 mg/2mLIntramuscularActavis Pharma Company2010-03-112018-10-31US flag
TrelstarInjection, powder, lyophilized, for suspension22.5 mg/2mLIntramuscularActavis Pharma Company2010-03-112018-10-31US flag
Trelstar3.75 mg/2mLIntramuscularVerity Pharmaceuticals Inc.2000-06-15Not applicableUS flag
TrelstarInjection, powder, for suspension, extended release3.75 mg / vialIntramuscularKnight Therapeutics Inc.2005-12-15Not applicableCanada flag

Categories

ATC Codes
L02AE04 — Triptorelin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom
Organic compounds
Super Class
Organic Polymers
Class
Polypeptides
Sub Class
Not Available
Direct Parent
Polypeptides
Alternative Parents
Peptides / Tyrosine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Tryptamines and derivatives / Serine and derivatives / Alpha amino acid amides
show 23 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 2-pyrrolidone / 3-alkylindole / Alcohol / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amphetamine or derivatives / Aromatic heteropolycyclic compound / Azacycle
show 48 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oligopeptide (CHEBI:63633)
Affected organisms
Not Available

Chemical Identifiers

UNII
9081Y98W2V
CAS number
57773-63-4
InChI Key
VXKHXGOKWPXYNA-PGBVPBMZSA-N
InChI
InChI=1S/C64H82N18O13/c1-34(2)23-46(56(88)75-45(13-7-21-69-64(66)67)63(95)82-22-8-14-52(82)62(94)72-31-53(65)85)76-58(90)48(25-36-28-70-42-11-5-3-9-40(36)42)78-57(89)47(24-35-15-17-39(84)18-16-35)77-61(93)51(32-83)81-59(91)49(26-37-29-71-43-12-6-4-10-41(37)43)79-60(92)50(27-38-30-68-33-73-38)80-55(87)44-19-20-54(86)74-44/h3-6,9-12,15-18,28-30,33-34,44-52,70-71,83-84H,7-8,13-14,19-27,31-32H2,1-2H3,(H2,65,85)(H,68,73)(H,72,94)(H,74,86)(H,75,88)(H,76,90)(H,77,93)(H,78,89)(H,79,92)(H,80,87)(H,81,91)(H4,66,67,69)/t44-,45-,46-,47-,48+,49-,50-,51-,52-/m0/s1
IUPAC Name
(2S)-N-[(2S)-5-carbamimidamido-1-[(2S)-2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]-2-[(2R)-2-[(2S)-2-[(2S)-3-hydroxy-2-[(2S)-2-[(2S)-3-(1H-imidazol-4-yl)-2-{[(2S)-5-oxopyrrolidin-2-yl]formamido}propanamido]-3-(1H-indol-3-yl)propanamido]propanamido]-3-(4-hydroxyphenyl)propanamido]-3-(1H-indol-3-yl)propanamido]-4-methylpentanamide
SMILES
CC(C)C[C@H](NC(=O)[C@@H](CC1=CNC2=CC=CC=C12)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=CNC=N1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)NCC(N)=O

References

General References
  1. Lahlou N, Carel JC, Chaussain JL, Roger M: Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab. 2000 Jul;13 Suppl 1:723-37. [Article]
  2. Padula AM: GnRH analogues--agonists and antagonists. Anim Reprod Sci. 2005 Aug;88(1-2):115-26. [Article]
KEGG Drug
D06247
PubChem Compound
25074470
PubChem Substance
310264898
ChemSpider
17290424
RxNav
38782
ChEBI
63633
ChEMBL
CHEMBL1201334
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Triptorelin
FDA label
Download (691 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentIdiopathic Short Stature (ISS)1
4CompletedNot AvailableProstate Cancer1
4CompletedTreatmentAssisted Reproduction1
4CompletedTreatmentEndometriosis1
4CompletedTreatmentEndometriosis / Infertility1
4CompletedTreatmentFatty Liver / Hypogonadism / Prostate Cancer / Syndrome, Metabolic1
4CompletedTreatmentFemale Infertility1
4CompletedTreatmentIn Vitro Fertilization (IVF)1
4CompletedTreatmentInfertility6
4CompletedTreatmentInfertility Indicated for ICSI1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntramuscular; Subcutaneous0.1 MG/ML
Injection, powder, for suspensionParenteral3.75 MG/2ML
Injection, powder, for suspension, extended release11.25 MG/2ML
Injection, powder, for suspension, extended release22.5 MG/2ML
SolutionSubcutaneous0.1 mg / mL
InjectionParenteral
Injection; solutionSubcutaneous
Injection, solutionSubcutaneous
Injection, powder, for suspensionIntramuscular3.75 mg
Powder3.75 mg
Injection, powder, for solutionIntramuscular; Subcutaneous3.75 mg/syringe
Injection, suspension, extended releaseIntramuscular; Subcutaneous
Capsule, extended releaseIntramuscular; Subcutaneous
SuspensionSubcutaneous
InjectionSubcutaneous100 mcg/ml
Injection, powder, for suspensionIntramuscular11.25 mg
Injection, powder, for suspension
Injection, powder, for suspensionIntramuscular
Injection, powder, for suspension, extended releaseIntramuscular; Subcutaneous
Injection, powder, for suspension, extended releaseIntramuscular11.25 mg
Injection, powder, for suspension, extended releaseIntramuscular3.75 mg
Injection, solution
Injection, solution0.1 MG/1ML
SolutionSubcutaneous95.6 mcg
Injection, powder, for suspension, extended releaseIntramuscular; Subcutaneous3.75 mg/ml
Injection, powder, lyophilized, for solution
Injection, powder, for suspensionParenteral
Injection, powder, lyophilized, for suspensionIntramuscular11.25 mg
Injection, powder, lyophilized, for suspensionIntramuscular22.5 mg
Injection, powder, lyophilized, for suspensionIntramuscular3.75 mg
Injection, powder, for suspension, extended releaseIntramuscular11.25 mg / vial
Injection, powder, for suspension, extended releaseIntramuscular22.5 mg / vial
Injection, powder, for suspension, extended releaseIntramuscular3.75 mg / vial
Injection, powder, lyophilized, for suspensionIntramuscular11.25 mg/2mL
Injection, powder, lyophilized, for suspensionIntramuscular22.5 mg/2mL
Injection, powder, lyophilized, for suspensionIntramuscular3.75 mg/2mL
KitIntramuscular11.25 mg/2mL
KitIntramuscular22.5 mg/2mL
KitIntramuscular3.75 mg/2mL
Injection, solutionParenteral
SolutionSubcutaneous0.1 mg/1ml
Injection, powder, for solutionIntramuscular; Subcutaneous3.75 mg/1vial
Injection, powder, for solutionIntramuscular; Subcutaneous0.1 mg/1vial
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5776885No1998-07-072015-07-07US flag
US10166181No2019-01-012029-02-10US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0305 mg/mLALOGPS
logP1.07ALOGPS
logP-3.6ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)9.49ChemAxon
pKa (Strongest Basic)11.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count18ChemAxon
Polar Surface Area487.92 Å2ChemAxon
Rotatable Bond Count33ChemAxon
Refractivity352.43 m3·mol-1ChemAxon
Polarizability135.23 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot 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
Actions
Agonist
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

Drug created on September 14, 2010 16:21 / Updated on October 24, 2021 16:00