Identification

Name
Triptorelin
Accession Number
DB06825
Type
Small Molecule
Groups
Approved, Vet approved
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.

Structure
Thumb
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
  • triptorelina
  • triptoreline
  • triptorelinum
External IDs
AY-25650 / CL 118,532 / CL-118532 / WY-42462
Product Ingredients
IngredientUNIICASInChI Key
Triptorelin acetate43OFW291R9140194-24-7HPPONSCISKROOD-OYLNGHKZSA-N
Triptorelin pamoate08AN7WA2G0124508-66-3ZBVJFYPGLGEMIN-OYLNGHKZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DecapeptylSolution0.1 mgSubcutaneousFerring Pharmaceuticals2012-08-09Not applicableCanada
TrelstarInjection, powder, for suspension, extended release11.25 mgIntramuscularAllergan Pharma Co.2005-12-15Not applicableCanada
TrelstarKit11.25 mg/2mLActavis Pharma Company2001-06-292018-10-31Us
TrelstarInjection, powder, lyophilized, for suspension11.25 mg/2mLIntramuscularActavis Pharma Company2001-06-292018-10-31Us
TrelstarKit11.25 mg/2mLAllergan2001-06-29Not applicableUs
TrelstarInjection, powder, for suspension, extended release3.75 mgIntramuscularAllergan Pharma Co.2005-12-15Not applicableCanada
TrelstarKit3.75 mg/2mLActavis Pharma Company2000-06-152018-10-31Us
TrelstarInjection, powder, lyophilized, for suspension3.75 mg/2mLIntramuscularActavis Pharma Company2000-06-152018-10-31Us
TrelstarKit3.75 mg/2mLAllergan2000-06-15Not applicableUs
TrelstarInjection, powder, for suspension, extended release22.5 mgIntramuscularAllergan Pharma Co.2013-10-16Not applicableCanada
International/Other Brands
Diphereline (Ferring Pharmaceuticals) / Gonapeptyl (Ferring Pharmaceuticals) / Variopeptyl (Varian Darou Pajooh)
Categories
UNII
9081Y98W2V
CAS number
57773-63-4
Weight
Average: 1311.473
Monoisotopic: 1310.630874772
Chemical Formula
C64H82N18O13
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

Pharmacology

Indication

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

Associated Conditions
Associated Therapies
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
Human
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.

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
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe therapeutic efficacy of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when used in combination with Triptorelin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Triptorelin.
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.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Triptorelin.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Triptorelin.
AICA ribonucleotideThe therapeutic efficacy of AICA ribonucleotide 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 Triptorelin is combined with Alimemazine.
AllicinThe therapeutic efficacy of Allicin can be decreased when used in combination with Triptorelin.
Food Interactions
Not Available

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]
External Links
KEGG Drug
D06247
PubChem Compound
25074470
PubChem Substance
310264898
ChemSpider
17290424
ChEBI
63633
ChEMBL
CHEMBL1201334
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Triptorelin
ATC Codes
L02AE04 — Triptorelin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (691 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingBasic ScienceInfertility, Female1
1, 2RecruitingTreatmentAdenocarcinoma, Prostate / Stage I Prostate Cancer / Stage IIA Prostate Cancer / Stage IIB Prostate Cancer / Stage III Prostate Cancer1
2Active Not RecruitingTreatmentBreast Cancer Invasive Nos1
2Active Not RecruitingTreatmentProstate Cancer1
2CompletedDiagnosticSystemic Lupus Erythematosus (SLE)1
2CompletedTreatmentInfertilities / Poor Ovarian Response2
2CompletedTreatmentProstate Cancer1
2RecruitingPreventionCancer, Breast1
2RecruitingSupportive CareAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage III Prostate Cancer / Stage IV Prostate Cancer1
2RecruitingTreatmentHIV-1-infection1
2RecruitingTreatmentProstate Cancer1
2RecruitingTreatmentSalivary Gland Cancers1
2RecruitingTreatmentSubfertility1
2SuspendedSupportive CareAdenocarcinoma, Prostate / Cancers / Prostate Cancer1
2TerminatedSupportive CareCancer, Breast / Hormone Changes / Therapeutic Agent Toxicity1
2TerminatedTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage IIIA Breast Cancer1
2TerminatedTreatmentProstate Cancer1
2, 3CompletedPreventionAlkylating Agents / Fertility Preservation / Malignant Lymphomas1
2, 3RecruitingTreatmentCastration-resistant Prostate Cancer Patients With Oligometastases1
2, 3RecruitingTreatmentInfertility, Female1
3Active Not RecruitingTreatmentCancer, Breast2
3Active Not RecruitingTreatmentCancer, Breast / Estrogen Receptor Positive Breast Cancer / Progesterone Receptor Positive Tumor / Recurrent Breast Carcinoma / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer1
3Active Not RecruitingTreatmentProstate Cancer4
3CompletedNot AvailableCancer, Breast / Sleep disorders and disturbances / Tiredness1
3CompletedDiagnosticProstate Cancer1
3CompletedSupportive CareCancer, Breast1
3CompletedTreatmentCentral Precocious Puberty (CPP)1
3CompletedTreatmentControlled Ovarian Stimulation1
3CompletedTreatmentEndometriosis1
3CompletedTreatmentInfertilities3
3CompletedTreatmentInfertilities / Polycystic Ovaries Syndrome1
3CompletedTreatmentProstate Cancer3
3CompletedTreatmentProstatic Neoplasms1
3CompletedTreatmentPuberty, Precocious2
3Not Yet RecruitingTreatmentOvarian Hyperstimulation Syndrome1
3RecruitingTreatmentEndometriosis1
3TerminatedNot AvailableInfertilities1
3TerminatedTreatmentCancer, Breast1
3Unknown StatusPreventionEndometriosis1
3Unknown StatusTreatmentProstate Cancer2
4Active Not RecruitingTreatmentIdiopathic Short Stature (ISS)1
4Active Not RecruitingTreatmentProstate Cancer1
4CompletedNot AvailableProstate Cancer1
4CompletedTreatmentEndometriosis1
4CompletedTreatmentEndometriosis / Infertilities1
4CompletedTreatmentFatty Liver / Hypogonadism / Metabolic Syndromes / Prostate Cancer1
4CompletedTreatmentInfertilities3
4CompletedTreatmentInfertilities / Premature Ovarian Failure (POF)1
4CompletedTreatmentInfertility Indicated for ICSI1
4CompletedTreatmentInvitro Fertilization1
4CompletedTreatmentOvarian Hyperstimulation Syndrome1
4RecruitingBasic ScienceGender Dysphoria1
4RecruitingSupportive CareInfertilities2
4RecruitingTreatmentEmbryo Transfer / Luteal Support1
4RecruitingTreatmentInfertilities3
4RecruitingTreatmentInfertility, Female1
4TerminatedPreventionOvarian Hyperstimulation Syndrome1
4TerminatedTreatmentAssisted Reproductive Technology therapy1
4TerminatedTreatmentProstate Cancer2
4Unknown StatusDiagnosticCentral Precocious Puberty (CPP) / Sexual Precocity1
4Unknown StatusPreventionCentral Precocious Puberty (CPP)1
4Unknown StatusPreventionOvarian Hyperstimulation Syndrome / Polycystic Ovaries Syndrome1
4Unknown StatusTreatmentInfertilities1
4Unknown StatusTreatmentInfertility, Female / Poor Responder1
Not AvailableActive Not RecruitingNot AvailableProstate Cancer1
Not AvailableActive Not RecruitingTreatmentEndometriosis / Infertilities1
Not AvailableCompletedNot AvailableDeep Infiltrating Endometriosis (DIE)1
Not AvailableCompletedNot AvailableImplantation, Embryo / Pregnancy1
Not AvailableCompletedNot AvailableNeonates / Pregnancy1
Not AvailableCompletedSupportive CareHodgkins Disease (HD) / Lymphoma, Hodgkins1
Not AvailableCompletedTreatmentEndometriotic Cysts1
Not AvailableCompletedTreatmentInfertilities3
Not AvailableCompletedTreatmentNormal Oocyte Donors1
Not AvailableCompletedTreatmentUterine Leiomyomas1
Not AvailableEnrolling by InvitationScreeningInfertility, Female / Single Nucleotide Polymorphism,GnRH Receptor, IVF1
Not AvailableNot Yet RecruitingNot AvailableInfertilities1
Not AvailableNot Yet RecruitingNot AvailableProstate Cancer1
Not AvailableNot Yet RecruitingTreatmentInfertilities2
Not AvailableNot Yet RecruitingTreatmentOvulatory Dysfunction / Subfertility, Female1
Not AvailableRecruitingNot AvailableInfertilities1
Not AvailableRecruitingNot AvailableProstate Cancer1
Not AvailableRecruitingDiagnosticIVF Treatment1
Not AvailableRecruitingOtherEmbryonic Quality Using MitoScore (DuoStim x Conventional Stimulation Protocol) / Infertility, Female / Potential Usefulness of the DuoStim Protocol / Rate of Euploid Embryos Per Cycle (DuoStim x Conventional Stimulation Protocol)1
Not AvailableRecruitingTreatmentEndometriosis1
Not AvailableRecruitingTreatmentProstate Cancer1
Not AvailableUnknown StatusPreventionInfertility and at High Risk of OHSS1
Not AvailableUnknown StatusTreatmentInfertility and at High Risk of OHSS1
Not AvailableUnknown StatusTreatmentWomen With Poor Ovarian Response1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionSubcutaneous0.1 mg
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
Kit11.25 mg/2mL
Kit22.5 mg/2mL
Kit3.75 mg/2mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5776885No1995-07-072015-07-07Us

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

Taxonomy

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
Polypeptide / Alpha peptide / Tyrosine or derivatives / Phenylalanine or derivatives / Histidine or derivatives / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Proline or derivatives / Triptan / Alpha-amino acid amide
show 48 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oligopeptide (CHEBI:63633)

Targets

Kind
Protein
Organism
Human
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 21, 2018 20:42