Triptorelin

Identification

Name
Triptorelin
Accession Number
DB06825
Description

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.

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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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
Learn about our commercial Adverse Effects data.
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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.

Affected organisms
Not Available
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.
AcebutololThe risk or severity of QTc prolongation can be increased when Triptorelin is combined with Acebutolol.
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.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
No interactions found.

Products

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
DecapeptylSolutionSubcutaneousFerring Pharmaceuticals2012-08-09Not applicableCanada flag
Trelstar22.5 mg/2mLIntramuscularVerity Pharmaceuticals Inc.2010-03-11Not applicableUS flag
TrelstarInjection, powder, lyophilized, for suspension3.75 mg/2mLIntramuscularActavis Pharma Company2000-06-152018-10-31US flag
Trelstar22.5 mg/2mLIntramuscularAllergan, Inc.2010-03-11Not applicableUS flag
TrelstarKit22.5 mg/2mLIntramuscularActavis Pharma Company2010-03-112018-10-31US flag
TrelstarInjection, powder, for suspension, extended release22.5 mgIntramuscularKnight Therapeutics Inc.2013-10-16Not applicableCanada flag
TrelstarInjection, powder, lyophilized, for suspension22.5 mg/2mLIntramuscularActavis Pharma Company2010-03-112018-10-31US flag
Trelstar11.25 mg/2mLIntramuscularVerity Pharmaceuticals Inc.2001-06-29Not applicableUS flag
Trelstar3.75 mg/2mLIntramuscularAllergan, Inc.2000-06-15Not applicableUS flag
Trelstar11.25 mg/2mLIntramuscularAllergan, Inc.2001-06-29Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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)

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[[email protected]](NC(=O)[[email protected]@H](CC1=CNC2=CC=CC=C12)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CC1=CNC2=C1C=CC=C2)NC(=O)[[email protected]](CC1=CNC=N1)NC(=O)[[email protected]@H]1CCC(=O)N1)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N1CCC[[email protected]]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. [PubMed:10969915]
  2. Padula AM: GnRH analogues--agonists and antagonists. Anim Reprod Sci. 2005 Aug;88(1-2):115-26. [PubMed:15955640]
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
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
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 / Metabolic Syndromes / Prostate Cancer1
4CompletedTreatmentFemale Infertility1
4CompletedTreatmentInfertility6
4CompletedTreatmentInfertility Indicated for ICSI1
4CompletedTreatmentInfertility / Premature Ovarian Failure (POF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solution0.1 MG/ML
Injection, powder, for suspension3.75 MG/2ML
Injection, powder, for suspension, extended releaseParenteral11.25 MG/2ML
Injection, powder, for suspension, extended releaseParenteral22.5 MG/2ML
SolutionSubcutaneous
Injection; solutionSubcutaneous0.1 mg/ml
Injection
Injection, powder, for suspensionIntramuscular3.75 mg
SuspensionSubcutaneous3.75 mg
Injection, powder, for suspensionIntramuscular11.25 mg
Injection0.1 mg/ml
SolutionSubcutaneous95.6 mcg
Powder
Injection, powder, for suspension, extended releaseIntramuscular11.25 mg
Injection, powder, for suspension, extended releaseIntramuscular22.5 mg
Injection, powder, for suspension, extended releaseIntramuscular3.75 mg
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
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5776885No1998-07-072015-07-07US flag
US10166181No2019-01-012029-02-10US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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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

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 10:21 / Updated on September 22, 2020 02:10

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