Identification

Name
Travoprost
Accession Number
DB00287  (APRD01271)
Type
Small Molecule
Groups
Approved
Description

Travoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a synthetic prostaglandin F2alpha analogue. [Wikipedia]

Structure
Thumb
Synonyms
  • Isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-{(1e,3R)-3-hydroxy-4-[(alpha,alpha,alpha-trifluoro-m-tolyl)oxy]-1-butenyl}cyclopentyl)-5-heptenoate
  • Travoprost
  • Travoprostum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IzbaSolution / drops30 μg/mlOphthalmicNovartis Europharm Limited2014-02-20Not applicableEu
IzbaSolution / drops30 μg/mlOphthalmicNovartis Europharm Limited2014-02-20Not applicableEu
IzbaSolution0.03 mg/1mLOphthalmicAlcon, Inc.2014-06-022014-06-02Us
IzbaSolution0.003 %OphthalmicNovartis2017-02-06Not applicableCanada
Sandoz TravoprostSolution0.004 %OphthalmicSandoz Canada Incorporated2014-08-15Not applicableCanada
TravatanSolution / drops40 μg/mlOphthalmicNovartis Europharm Limited2001-11-27Not applicableEu
TravatanSolution0.04 mg/1mLOphthalmicAlcon, Inc.2001-03-162010-07-01Us
TravatanSolution / drops40 μg/mlOphthalmicNovartis Europharm Limited2001-11-27Not applicableEu
TravatanSolution / drops40 μg/mlOphthalmicNovartis Europharm Limited2001-11-27Not applicableEu
TravatanSolution0.004 %OphthalmicAlcon, Inc.2001-11-132010-11-16Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-travoprost ZSolution0.004 %OphthalmicApotex Corporation2014-08-14Not applicableCanada
Mylan-travoprost ZSolution0.004 %OphthalmicMylan PharmaceuticalsNot applicableNot applicableCanada
PMS-travoprost ZSolution0.004 %OphthalmicPharmascience IncNot applicableNot applicableCanada
Teva-travoprost Z Ophthalmic SolutionSolution0.004 %OphthalmicTeva2014-08-18Not applicableCanada
Travoprost Ophthalmic Solution 0.004%Solution0.04 mg/1mLOphthalmicPar Pharmaceutical2013-04-152019-10-31Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Apo-travoprost-timopTravoprost (0.004 %) + Timolol (0.5 %)SolutionOphthalmicApotex CorporationNot applicableNot applicableCanada
Duotrav PqTravoprost (0.004 %) + Timolol (0.5 %)SolutionOphthalmicNovartis2006-04-11Not applicableCanada
Sandoz Travoprost / Timolol PqTravoprost (0.004 %) + Timolol (0.5 %)SolutionOphthalmicSandoz Canada IncorporatedNot applicableNot applicableCanada
International/Other Brands
Travatan / Travatan Z / Travo-Z
Categories
UNII
WJ68R08KX9
CAS number
157283-68-6
Weight
Average: 500.5477
Monoisotopic: 500.238573467
Chemical Formula
C26H35F3O6
InChI Key
MKPLKVHSHYCHOC-AHTXBMBWSA-N
InChI
InChI=1S/C26H35F3O6/c1-17(2)35-25(33)11-6-4-3-5-10-21-22(24(32)15-23(21)31)13-12-19(30)16-34-20-9-7-8-18(14-20)26(27,28)29/h3,5,7-9,12-14,17,19,21-24,30-32H,4,6,10-11,15-16H2,1-2H3/b5-3-,13-12+/t19-,21-,22-,23+,24-/m1/s1
IUPAC Name
propan-2-yl (5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-en-1-yl]cyclopentyl]hept-5-enoate
SMILES
CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(=C1)C(F)(F)F

Pharmacology

Indication

Ophthalmic solution used for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.

Associated Conditions
Pharmacodynamics

Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analogue that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid. The travoporst free acid is potent and highly selective for the FP prostanoid receptor.

Mechanism of action

Travoprost free acid is a selective FP prostanoid receptor agonist and is believed to reduce intraocular pressure by increasing the drainage of aqueous humor, which is done primarily through increased uveoscleral outflow and to a lesser extent, trabecular outflow facility.

TargetActionsOrganism
AProstaglandin F2-alpha receptor
agonist
Human
Absorption

Systemically absorbed when administered to the eye.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α(carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14 double bond.

Route of elimination

Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.

Half life

Terminal elimination half-life of travoprost free acid is 45 minutes.

Clearance
Not Available
Toxicity

Symptoms of overexposure include irritation to the skin, eyes, nose, throat, and respiratory tract.

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

Interactions

Drug Interactions
DrugInteraction
AcebutololTravoprost may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Travoprost can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Travoprost can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Travoprost can be decreased when used in combination with Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Travoprost can be decreased when used in combination with Alclofenac.
AliskirenTravoprost may increase the hypotensive activities of Aliskiren.
AlminoprofenThe therapeutic efficacy of Travoprost can be decreased when used in combination with Alminoprofen.
AlprenololTravoprost may increase the hypotensive activities of Alprenolol.
AmbrisentanTravoprost may increase the hypotensive activities of Ambrisentan.
AminophenazoneThe therapeutic efficacy of Travoprost can be decreased when used in combination with Aminophenazone.
Food Interactions
Not Available

References

General References
  1. Lim KS, Nau CB, O'Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. doi: 10.1016/j.ophtha.2007.07.002. [PubMed:18452763]
  2. Costagliola C, dell'Omo R, Romano MR, Rinaldi M, Zeppa L, Parmeggiani F: Pharmacotherapy of intraocular pressure - part II. Carbonic anhydrase inhibitors, prostaglandin analogues and prostamides. Expert Opin Pharmacother. 2009 Dec;10(17):2859-70. doi: 10.1517/14656560903300129. [PubMed:19929706]
  3. Ferrari G, Scagliotti GV: Serum and urinary vascular endothelial growth factor levels in non-small cell lung cancer patients. Eur J Cancer. 1996 Dec;32A(13):2368-9. [PubMed:9038626]
  4. Toris CB, Gabelt BT, Kaufman PL: Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction. Surv Ophthalmol. 2008 Nov;53 Suppl1:S107-20. doi: 10.1016/j.survophthal.2008.08.010. [PubMed:19038618]
  5. Arranz-Marquez E, Teus MA: Prostanoids for the management of glaucoma. Expert Opin Drug Saf. 2008 Nov;7(6):801-8. doi: 10.1517/14740330802465474 . [PubMed:18983226]
External Links
Human Metabolome Database
HMDB0014432
KEGG Drug
D01964
PubChem Compound
5282226
PubChem Substance
46507637
ChemSpider
4445407
ChEBI
746859
ChEMBL
CHEMBL1200799
Therapeutic Targets Database
DAP000274
PharmGKB
PA164781371
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Travoprost
ATC Codes
S01EE04 — Travoprost
AHFS Codes
  • 52:40.28 — Prostaglandin Analogs
FDA label
Download (36.8 KB)
MSDS
Download (72.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentGlaucoma / Ocular Hypertension1
2Active Not RecruitingTreatmentGlaucoma and Ocular Hypertension1
2CompletedTreatmentGlaucoma / Glaucoma or Ocular Hypertension and / Ocular Hypertension / Ocular Surface Disease1
2CompletedTreatmentGlaucoma / Ocular Hypertension2
2CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
2CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)5
3CompletedTreatmentGlaucoma, Angle-Closure / Ocular Hypertension1
3CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
3CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)11
3RecruitingPreventionGlaucoma1
3RecruitingTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
3TerminatedTreatmentGlaucoma / Ocular Hypertension2
3Unknown StatusTreatmentGlaucoma2
3WithdrawnTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
4Active Not RecruitingTreatmentOpen-angle Glaucoma (OAG)2
4CompletedSupportive CareDry Eye Syndrome (DES)1
4CompletedTreatmentAnterior Uveitis (AU) / Cystoid Macular Edema1
4CompletedTreatmentApplication Site Pigmentation Changes / Glaucoma1
4CompletedTreatmentGlaucoma5
4CompletedTreatmentGlaucoma, Angle-Closure1
4CompletedTreatmentGlaucoma / Ocular Hypertension9
4CompletedTreatmentGlaucoma / Ocular Hypertension / Open-angle Glaucoma (OAG)1
4CompletedTreatmentHyperemia / Intraocular Pressure1
4CompletedTreatmentIntraocular Pressure1
4CompletedTreatmentNormal Tension Glaucoma / Ocular Hypertension1
4CompletedTreatmentOcular Hypertension1
4CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)3
4CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)5
4CompletedTreatmentOpen-angle Glaucoma (OAG)2
4Not Yet RecruitingTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
4RecruitingTreatmentGlaucoma1
4TerminatedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
4TerminatedNot AvailableOpen-angle Glaucoma (OAG)1
4TerminatedTreatmentGlaucoma1
4TerminatedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableCompletedNot AvailableOcular Dryness / Ocular Hypertension / Ocular Irritation / Open-angle Glaucoma (OAG)1
Not AvailableCompletedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableCompletedDiagnosticGlaucoma / Ocular Hypertension1
Not AvailableCompletedTreatmentGlaucoma, Primary Open Angle (POAG)1
Not AvailableCompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG) / Pseudoexfoliation Syndrome1
Not AvailableUnknown StatusTreatmentOcular Hypertension / Primary Glaucoma1
Not AvailableWithdrawnTreatmentGlaucoma, Neovascular1

Pharmacoeconomics

Manufacturers
  • Alcon inc
Packagers
  • Alcon Laboratories
  • Liberty Carton Co.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
SolutionOphthalmic0.003 %
SolutionOphthalmic0.03 mg/1mL
Solution / dropsOphthalmic30 μg/ml
SolutionOphthalmic
SolutionOphthalmic0.004 %
SolutionOphthalmic0.04 mg/1mL
Solution / dropsOphthalmic40 μg/ml
Solution / dropsOphthalmic0.04 mg/1mL
Prices
Unit descriptionCostUnit
Travatan 0.004% Solution 5ml Bottle190.82USD bottle
Travatan Z 0.004% Solution 5ml Bottle190.82USD bottle
Travatan 0.004% Solution 2.5ml Bottle95.41USD bottle
Travatan Z 0.004% Solution 2.5ml Bottle95.41USD bottle
Travatan 0.004% eye drop45.87USD ml
Travatan z 0.004% eye drop36.7USD ml
Travatan 0.004 % Solution12.18USD ml
Travatan Z 0.004 % Solution12.18USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5631287No1994-12-222014-12-22Us
US6503497No1995-05-062012-05-06Us
CA2181172No2003-04-292015-12-19Canada
CA2129287No2002-05-142014-08-02Canada
US8268299No2009-10-132029-10-13Us
US8323630No2007-09-202027-09-20Us
US8388941No2007-09-202027-09-20Us
US9144561No2009-03-132029-03-13Us
US8722735No2009-10-102029-10-10Us
US8178582No2009-10-102029-10-10Us
US8754123No2009-05-192029-05-19Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubility>16 mg/ml at 25.0°CNot Available
logP4.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00759 mg/mLALOGPS
logP4.02ALOGPS
logP3.84ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)13.95ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area96.22 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity127.86 m3·mol-1ChemAxon
Polarizability51.61 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9857
Blood Brain Barrier+0.887
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.5907
P-glycoprotein inhibitor INon-inhibitor0.8237
P-glycoprotein inhibitor IINon-inhibitor0.6435
Renal organic cation transporterNon-inhibitor0.8856
CYP450 2C9 substrateNon-substrate0.8327
CYP450 2D6 substrateNon-substrate0.8383
CYP450 3A4 substrateSubstrate0.652
CYP450 1A2 substrateNon-inhibitor0.728
CYP450 2C9 inhibitorNon-inhibitor0.7607
CYP450 2D6 inhibitorNon-inhibitor0.9125
CYP450 2C19 inhibitorNon-inhibitor0.6844
CYP450 3A4 inhibitorNon-inhibitor0.8546
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7657
Ames testNon AMES toxic0.7427
CarcinogenicityNon-carcinogens0.9088
BiodegradationNot ready biodegradable0.9726
Rat acute toxicity3.5280 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9744
hERG inhibition (predictor II)Non-inhibitor0.6722
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Eicosanoids
Direct Parent
Prostaglandins and related compounds
Alternative Parents
Trifluoromethylbenzenes / Phenoxy compounds / Phenol ethers / Fatty acid esters / Alkyl aryl ethers / Cyclopentanols / Cyclic alcohols and derivatives / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organofluorides
show 4 more
Substituents
Prostaglandin skeleton / Trifluoromethylbenzene / Phenoxy compound / Phenol ether / Alkyl aryl ether / Fatty acid ester / Monocyclic benzene moiety / Benzenoid / Cyclopentanol / Cyclic alcohol
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carboxylic ester, prostaglandins Falpha, (trifluoromethyl)benzenes (CHEBI:746859)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Prostaglandin f receptor activity
Specific Function
Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis...
Gene Name
PTGFR
Uniprot ID
P43088
Uniprot Name
Prostaglandin F2-alpha receptor
Molecular Weight
40054.1 Da
References
  1. Ota T, Aihara M, Narumiya S, Araie M: The effects of prostaglandin analogues on IOP in prostanoid FP-receptor-deficient mice. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4159-63. [PubMed:16249494]
  2. Thieme H, Schimmat C, Munzer G, Boxberger M, Fromm M, Pfeiffer N, Rosenthal R: Endothelin antagonism: effects of FP receptor agonists prostaglandin F2alpha and fluprostenol on trabecular meshwork contractility. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):938-45. [PubMed:16505027]
  3. Lim KS, Nau CB, O'Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. doi: 10.1016/j.ophtha.2007.07.002. [PubMed:18452763]
  4. Neacsu AM: [Receptors involved in the mechanism of action of topical prostaglandines]. Oftalmologia. 2009;53(2):3-7. [PubMed:19697832]
  5. Costagliola C, dell'Omo R, Romano MR, Rinaldi M, Zeppa L, Parmeggiani F: Pharmacotherapy of intraocular pressure - part II. Carbonic anhydrase inhibitors, prostaglandin analogues and prostamides. Expert Opin Pharmacother. 2009 Dec;10(17):2859-70. doi: 10.1517/14656560903300129. [PubMed:19929706]
  6. Ferrari G, Scagliotti GV: Serum and urinary vascular endothelial growth factor levels in non-small cell lung cancer patients. Eur J Cancer. 1996 Dec;32A(13):2368-9. [PubMed:9038626]
  7. Toris CB, Gabelt BT, Kaufman PL: Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction. Surv Ophthalmol. 2008 Nov;53 Suppl1:S107-20. doi: 10.1016/j.survophthal.2008.08.010. [PubMed:19038618]
  8. Arranz-Marquez E, Teus MA: Prostanoids for the management of glaucoma. Expert Opin Drug Saf. 2008 Nov;7(6):801-8. doi: 10.1517/14740330802465474 . [PubMed:18983226]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:40