Tafluprost

Identification

Summary

Tafluprost is an ophthalmic prostaglandin analog used to lower intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Brand Names
Zioptan
Generic Name
Tafluprost
DrugBank Accession Number
DB08819
Background

A prostaglandin analogue ester prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. Chemically, tafluprost is a fluorinated analog of prostaglandin F2-alpha. Tafluprost was approved for use in the U.S. on February 10, 2012.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 452.5313
Monoisotopic: 452.237430608
Chemical Formula
C25H34F2O5
Synonyms
  • Tafluprost
External IDs
  • AFP-168
  • MK-2452

Pharmacology

Indication

Tafluprost is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofElevated intraocular pressure••••••••••••
Management ofElevated intraocular pressure••••••••••••
Used in combination to treatOcular hypertensionCombination Product in combination with: Timolol (DB00373)••••••••••••••••••••
Used in combination to treatOcular hypertensionCombination Product in combination with: Timolol (DB00373)••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Tafluprost is a novel prostaglandin analog with a high affinity for the fluoroprostaglandin (FP) receptor PGF2α. Tafluprost has an affinity for the FP receptor that is approximately 12 times higher than that of the carboxylic acid of latanoprost, but with almost no potential to bind to other receptors.

Mechanism of action

Tafluprost acid is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and humans suggest that the main mechanism of action is increased uveoscleral outflow.

TargetActionsOrganism
AProstaglandin F2-alpha receptor
agonist
Humans
Absorption

Following instillation, tafluprost is absorbed through the cornea and is hydrolyzed to the biologically active acid metabolite, tafluprost acid. Tafluprost is an ester which makes the drug lipophillic enough to be quickly absorbed through. When administered to the eye, the peak plasma concentration (Cmax) and time to peak plasma concentration (Tmax) of tafluprost acid in healthy subjects was 26 pg/mL and 10 minutes respectively. a AUC, tafluprost acid = 394 pgmin/mL - 432 pgmin/mL.

Volume of distribution

The highest concentration of tafluprost acid was found in the cornea and conjunctiva.

Protein binding

Not Available

Metabolism

Tafluprost is an ester prodrug which is rapidly hydrolyzed by corneal esterases to form its biologically active acid metabolite. Tafluprost acid is further metabolized via fatty acid β-oxidation and phase II conjugation into 1,2,3,4-tetranor acid.

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Route of elimination

Mean plasma tafluprost acid concentrations were below the limit of quantification of the bioanalytical assay (10 pg/mL) at 30 minutes following topical ocular administration of tafluprost 0.0015% ophthalmic solution. In male rats, it was observed that tafluprost was excreted into the feces.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Most common ocular adverse reaction is conjunctival hyperemia (range 4% – 20%).

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
AceclofenacThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Alclofenac.
AminophenazoneThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Aminophenazone.
Food Interactions
No interactions found.

Products

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International/Other Brands
Taflotan (Regeneron Pharmaceuticals)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SaflutanSolution4.5 mcg / 0.3 mLOphthalmicPurdue PharmaNot applicableNot applicableCanada flag
ZioptanSolution / drops0.0045 mg/0.3mLOphthalmicAkorn2014-11-26Not applicableUS flag
ZioptanSolution / drops0.015 mg/1mLOphthalmicThea Pharma Inc.2022-10-28Not applicableUS flag
ZioptanSolution0.0045 mg/0.3mLOphthalmicMerck Sharp & Dohme Limited2012-02-102016-06-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TafluprostSolution / drops0.015 mg/1mLOphthalmicIngenus Pharmaceuticals, LLC2024-04-05Not applicableUS flag
TafluprostSolution / drops0.0045 mg/0.3mLOphthalmicMicro Labs Limited2022-11-18Not applicableUS flag
TafluprostSolution0.0045 mg/0.3mLOphthalmicThe Ritedose Corporation2022-12-05Not applicableUS flag
TafluprostSolution / drops0.0045 mg/0.3mLOphthalmicSandoz Inc2022-12-05Not applicableUS flag
Tafluprost OphthalmicSolution / drops0.0045 mg/0.3mLOphthalmicPrasco Laboratories2022-11-18Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
LOYADATafluprost (15 µg/ml) + Timolol (5 MG/ML)Solution / dropsOphthalmicSanten Italy Srl2015-04-08Not applicableItaly flag
LOYADATafluprost (15 µg/ml) + Timolol (5 MG/ML)Solution / dropsOphthalmicSanten Italy Srl2015-04-08Not applicableItaly flag
TAPCOM ophthalmic solutionTafluprost (15 µg/mL) + Timolol maleate (5 mg/mL)Solution / dropsOphthalmicSANTEN PHARMA MALAYSIA SDN. BHD.2020-09-082024-06-28Malaysia flag
TAPCOM-S OPHTHALMIC SOLUTIONTafluprost (0.015 mg/ml) + Timolol maleate (5.00 mg/ml)SolutionOphthalmicSANTEN PHARMACEUTICAL ASIA PTE. LTD.2016-02-08Not applicableSingapore flag
Taptiqom 15 Mikrogramm/ml + 5 mg/ml Augentropfen, Lösung im EinzeldosisbehältnisTafluprost (15 mcg/ml) + Timolol (5 mg/ml)Solution / dropsOphthalmicSanten Oy2015-02-24Not applicableAustria flag

Categories

ATC Codes
S01EE05 — Tafluprost
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Phenoxy compounds / Phenol ethers / Fatty acid esters / Alkyl aryl ethers / Cyclopentanols / Cyclic alcohols and derivatives / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organofluorides / Organic oxides
show 3 more
Substituents
Alcohol / Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Aromatic homomonocyclic compound / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic alcohol
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organofluorine compound, carboxylic ester, prostaglandins Falpha (CHEBI:66899)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1O6WQ6T7G3
CAS number
209860-87-7
InChI Key
WSNODXPBBALQOF-VEJSHDCNSA-N
InChI
InChI=1S/C25H34F2O5/c1-18(2)32-24(30)13-9-4-3-8-12-20-21(23(29)16-22(20)28)14-15-25(26,27)17-31-19-10-6-5-7-11-19/h3,5-8,10-11,14-15,18,20-23,28-29H,4,9,12-13,16-17H2,1-2H3/b8-3-,15-14+/t20-,21-,22+,23-/m1/s1
IUPAC Name
propan-2-yl (5Z)-7-[(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl]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(F)(F)COC1=CC=CC=C1

References

General References
  1. Papadia M, Bagnis A, Scotto R, Traverso CE: Tafluprost for glaucoma. Expert Opin Pharmacother. 2011 Oct;12(15):2393-401. doi: 10.1517/14656566.2011.606810. [Article]
  2. Pantcheva MB, Seibold LK, Awadallah NS, Kahook MY: Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011 Sep;28(9):707-15. doi: 10.1007/s12325-011-0055-8. Epub 2011 Aug 18. [Article]
  3. Takagi Y, Nakajima T, Shimazaki A, Kageyama M, Matsugi T, Matsumura Y, Gabelt BT, Kaufman PL, Hara H: Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004 Apr;78(4):767-76. [Article]
  4. Fukano Y, Kawazu K: Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats. Drug Metab Dispos. 2009 Aug;37(8):1622-34. doi: 10.1124/dmd.108.024885. Epub 2009 May 28. [Article]
  5. FDA Approved Drug Products: ZIOPTAN (tafluprost) ophthalmic [Link]
Human Metabolome Database
HMDB0015704
KEGG Drug
D06274
PubChem Compound
9868491
PubChem Substance
175427102
ChemSpider
8044182
RxNav
1244607
ChEBI
66899
ChEMBL
CHEMBL1963683
ZINC
ZINC000013912394
PharmGKB
PA165958432
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tafluprost
FDA label
Download (274 KB)
MSDS
Download (22.7 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableOcular Hypertension, Primary Open-angle Glaucoma (POAG)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableOcular Hypertension, Primary Open-angle Glaucoma (POAG) / Ocular Surface Disease1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentOcular Hypertension, Primary Open-angle Glaucoma (POAG)1somestatusstop reasonjust information to hide
4CompletedTreatmentGlaucoma1somestatusstop reasonjust information to hide
4CompletedTreatmentGlaucoma / Ocular Hypertension1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOphthalmic15.000 mcg
SolutionOphthalmic4.5 mcg / 0.3 mL
Solution / dropsOphthalmic15 MICROGRAMMI/ML
Solution / dropsOphthalmic15 mcg/ml
Solution / dropsOphthalmic
SolutionOphthalmic0.015 mg/mL
Solution / dropsOphthalmic0015 MG/ML
Solution / drops; suspension / dropsOphthalmic15 UG/ML
SolutionOphthalmic0.015 mg
SolutionOphthalmic
Solution / dropsOphthalmic
Solution / drops; suspension / dropsOphthalmic
SolutionOphthalmic0.0045 mg/0.3mL
Solution / dropsOphthalmic0.0045 mg/0.3mL
Solution / dropsOphthalmic0.015 mg/1mL
LiquidOphthalmic15 mcg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5886035No1999-03-232017-12-18US flag
US9999593No2018-06-192029-05-28US flag
US10864159No2020-12-152029-05-28US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)87.5 °CNot Available
boiling point (°C)100°C Not Available
water solubilityInsoluble FDA label
logP4.05Not Available
pKa5.5-6.7FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00528 mg/mLALOGPS
logP4.46ALOGPS
logP4.29Chemaxon
logS-4.9ALOGPS
pKa (Strongest Acidic)14.51Chemaxon
pKa (Strongest Basic)-2.9Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area75.99 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity120.59 m3·mol-1Chemaxon
Polarizability47.77 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9644
Blood Brain Barrier+0.8687
Caco-2 permeable+0.5372
P-glycoprotein substrateSubstrate0.5871
P-glycoprotein inhibitor INon-inhibitor0.9015
P-glycoprotein inhibitor IINon-inhibitor0.7888
Renal organic cation transporterNon-inhibitor0.8711
CYP450 2C9 substrateNon-substrate0.8086
CYP450 2D6 substrateNon-substrate0.854
CYP450 3A4 substrateSubstrate0.6508
CYP450 1A2 substrateNon-inhibitor0.75
CYP450 2C9 inhibitorNon-inhibitor0.7344
CYP450 2D6 inhibitorNon-inhibitor0.9056
CYP450 2C19 inhibitorNon-inhibitor0.6873
CYP450 3A4 inhibitorNon-inhibitor0.8038
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7418
Ames testNon AMES toxic0.7286
CarcinogenicityNon-carcinogens0.9028
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity3.7129 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9787
hERG inhibition (predictor II)Non-inhibitor0.7362
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-MSsplash10-052f-4439700000-5f902e96f572f76cc593
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05o3-0009200000-57e5650afc06b8ef9365
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udl-3006900000-d9e3c2f668ee28744afd
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00dl-3019000000-7f23f368b49615e2d7ab
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00mo-1019400000-aecd74fa7227cbdbe538
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9123000000-e5f513d87ac7705df216
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fb9-3960100000-314446c2b5d734f9c56d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-227.7165607
predicted
DarkChem Lite v0.1.0
[M-H]-216.11147
predicted
DeepCCS 1.0 (2019)
[M+H]+229.4990607
predicted
DarkChem Lite v0.1.0
[M+H]+218.00685
predicted
DeepCCS 1.0 (2019)
[M+Na]+227.5501607
predicted
DarkChem Lite v0.1.0
[M+Na]+223.66032
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General 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 in the corpus luteum (By similarity). Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and isoform 5 are proposed to be a receptor for prostamides including the synthetic analog bimatoprost
Specific Function
prostaglandin F receptor activity
Gene Name
PTGFR
Uniprot ID
P43088
Uniprot Name
Prostaglandin F2-alpha receptor
Molecular Weight
40054.1 Da
References
  1. Pantcheva MB, Seibold LK, Awadallah NS, Kahook MY: Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011 Sep;28(9):707-15. doi: 10.1007/s12325-011-0055-8. Epub 2011 Aug 18. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function
enzyme binding
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Roh YJ, Park YG, Kang S, Kim SY, Moon JI: Effects of AFP-172 on COX-2-induced angiogenic activities on human umbilical vein endothelial cells. Graefes Arch Clin Exp Ophthalmol. 2012 Dec;250(12):1765-75. doi: 10.1007/s00417-012-2125-2. Epub 2012 Aug 22. [Article]

Drug created at February 24, 2012 17:29 / Updated at October 07, 2024 13:58