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
Thumb
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.

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
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

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.

Hover over products below to view reaction partners

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
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

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.
AntipyrineThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Antipyrine.
AntrafenineThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Antrafenine.
BalsalazideThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Balsalazide.
BenorilateThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Benorilate.
BenoxaprofenThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Benoxaprofen.
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
International/Other Brands
Taflotan (Regeneron Pharmaceuticals)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SaflutanSolution4.5 mcg / 0.3 mLOphthalmicPurdue PharmaNot applicableNot applicableCanada flag
ZioptanSolution0.0045 mg/0.3mLOphthalmicMerck Sharp & Dohme Limited2012-02-102016-06-30US flag
ZioptanSolution / drops0.0045 mg/0.3mLOphthalmicAkorn, Inc.2014-11-26Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
แทพคอมTafluprost (1.5 mg/100mL) + Timolol (500 mg/100mL)Solution / dropsOphthalmicบริษัท ซันเท็น (ประเทศไทย) จำกัด2018-11-06Not applicableThailand flag
แทพคอม-เอสTafluprost (1.5 mg/100mL) + Timolol (500 mg/100mL)Solution / dropsOphthalmicบริษัท ซันเท็น (ประเทศไทย) จำกัด2018-11-06Not applicableThailand 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
PhaseStatusPurposeConditionsCount
4CompletedTreatmentGlaucoma1
4CompletedTreatmentGlaucoma / Ocular Hypertension1
4CompletedTreatmentGlaucoma / Ocular Hypertension / Ocular Hypertension, Primary Open-angle Glaucoma (POAG)1
4CompletedTreatmentGlaucoma / Ocular Surface Disease1
4CompletedTreatmentOcular Hypertension, Primary Open-angle Glaucoma (POAG)1
4CompletedTreatmentOcular Hypertension / Ocular Hypertension, Primary Open-angle Glaucoma (POAG)2
4CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)2
4CompletedTreatmentOpen Angle Glaucoma (OAG)1
4RecruitingTreatmentGlaucoma1
4Unknown StatusTreatmentGlaucoma / Ocular Hypertension1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOphthalmic4.5 mcg / 0.3 mL
Solution / dropsOphthalmic15 MICROGRAMMI/ML
Solution / dropsOphthalmic
SolutionOphthalmic0.015 mg/mL
Solution / drops; suspension / dropsOphthalmic15 UG/ML
Solution / dropsOphthalmic
Solution / drops; suspension / dropsOphthalmic
SolutionOphthalmic0.0045 mg/0.3mL
Solution / dropsOphthalmic0.0045 mg/0.3mL
LiquidOphthalmic15 mcg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5886035No1999-03-232017-12-18US flag
US9999593No2018-06-192029-05-28US flag
US10864159No2009-05-282029-05-28US 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-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

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
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. 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
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
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 on February 24, 2012 17:29 / Updated on September 27, 2021 07:54