Tafluprost: Difference between revisions

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{{Short description|Chemical compound}}
{{Use dmy dates|date=April 2024}}
{{Drugbox
{{Drugbox
| IUPAC_name = isopropyl (5''Z'')-7-{(1''R'',2''R'',3''R'',5''S'')-2-[(1''E'')-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl}hept-5-enoate
| IUPAC_name = Isopropyl (5''Z'')-7-<nowiki/>{(1''R'',2''R'',3''R'',5''S'')-2-[(1''E'')-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl}hept-5-enoate
| image = Tafluprost_structure.svg
| image = Tafluprost_structure.svg


<!--Clinical data-->
<!--Clinical data-->
| tradename = Saflutan, Taflotan, Tapros, Zioptan
| tradename = Saflutan, Taflotan, Zioptan
| Drugs.com = {{drugs.com|international|tafluprost}}
| Drugs.com = {{drugs.com|MTM|tafluprost-ophthalmic}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = C
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = Rx-only
| legal_CA_comment =<ref>{{cite web |title=Product monograph |url=https://pdf.hres.ca/dpd_pm/00058012.PDF |website=hres.ca |access-date=6 April 2024}}</ref>
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = Rx-only
| legal_US = Rx-only
| legal_status =
| legal_status =
| routes_of_administration = Topical ([[eye drop]]s)
| routes_of_administration = Topical [[Ophthalmic drug administration|eye drops]]


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism = Activation by ester [[hydrolysis]], deactivation by [[beta oxidation]]
| metabolism =
| metabolites =
⚫
| elimination_half-life =
| onset = 2–4 hrs
⚫
| excretion =
⚫
| elimination_half-life =
| duration_of_action = ≥ 24 hrs
⚫
| excretion =


<!--Identifiers-->
<!--Identifiers-->
Line 31: Line 36:
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 66899
| ChEBI = 66899
| DrugBank =
| DrugBank = DB08819
| ChEMBL = 1963683
| ChEMBL = 1963683
| ChemSpiderID = 8044182
| ChemSpiderID = 8044182
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1O6WQ6T7G3
| UNII = 1O6WQ6T7G3
| KEGG = D06274


<!--Chemical data-->
<!--Chemical data-->
| chemical_formula =
| C=25 | H=34 | F=2 | O=5
| C=25 | H=34 | F=2 | O=5
| molecular_weight = 452.531266 g/mol
| smiles = CC(C)OC(=O)CCC\C=C/CC(C(O)CC1O)C1\C=C\C(F)(F)COc2ccccc2
| smiles = CC(C)OC(=O)CCC\C=C/CC(C(O)CC1O)C1\C=C\C(F)(F)COc2ccccc2
| StdInChI = 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
| StdInChI = 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
| StdInChIKey = WSNODXPBBALQOF-VEJSHDCNSA-N
}}
}}


'''Tafluprost''' (trade names '''Taflotan''', marketed by [[Santen Pharmaceutical]] and '''Zioptan''', by Merck (U.S.)) is a [[prostaglandin analogue]] used topically (as [[eye drop]]s) to control the progression of [[glaucoma]] and in the management of [[ocular hypertension]]. It reduces [[intraocular pressure]] by increasing the outflow of [[Aqueous humour|aqueous fluid]] from the eyes.<ref>Schubert-Zsilavecz, M, Wurglics, M, ''Neue Arzneimittel 2008/2009''</ref><ref>[http://www.santen.eu/index/news/07052008_Santen_Oy_Receives_Marketing_Authorization.html Santen Home Page]</ref>
'''Tafluprost''' (trade names '''Taflotan''' by [[Santen Pharmaceutical]], '''Zioptan''' by Merck in the US and '''Saflutan''' by Mundipharma in Australia) is a [[prostaglandin analogue]]. It is used topically (as [[eye drop]]s) to control the progression of [[open-angle glaucoma]] and in the management of [[ocular hypertension]], alone or in combination with other medication. It reduces [[intraocular pressure]] by increasing the outflow of [[Aqueous humour|aqueous fluid]] from the eyes.<ref name="PPA" /><ref name="AC" />


==Adverse effects==
Taflotan contains 15 µg/ml Tafluprost. ''Taflotan sine'' is a preservative-free, single-dose formulation containing 0.3 ml per dose.<ref>[http://www.gelbe-liste.de/pharmindex/praeparat/taflotan-sine-15-mikrogrammml-augentropfen-in-einzeldosen-santen-gmbh/ Gelbe Liste (in German)]</ref>
The most common side effect is [[conjunctival hyperemia]], which occurs in 4 to 20% of patients. Less common side effects include stinging of the eyes, headache, and [[respiratory infection]]s. Rare side effects are [[dyspnoea]] (breathing difficulties), worsening of [[asthma]], and [[macular oedema]].<ref name="PPA" /><ref name="AC" /><ref name="Dinnendahl" />


==References==
== Interactions ==
⚫
{{Reflist}}


[[Nonsteroidal anti-inflammatory drug]]s (NSAIDs) can either reduce or increase the effect of tafluprost.<ref name="PPA" /> [[Timolol]] eye drops, a common kind of glaucoma medication, does not negatively interact with this drug.<ref name="AC" />

No interactions with systemic (for example, oral) drugs are expected because tafluprost does not reach relevant concentrations in the bloodstream.<ref name="AC" /><ref name="Dinnendahl" />

==Pharmacology==
===Mechanism of action===
Tafluprost is a [[prodrug]] of the active substance, tafluprost acid, a [[structural analogue|structural]] and [[Functional analog (chemistry)|functional analogue]] of [[prostaglandin F2α|prostaglandin F<sub>2α</sub>]] (PGF<sub>2α</sub>). Tafluprost acid is a selective [[agonist]] at the [[prostaglandin F receptor]], increasing outflow of aqueous fluid from the eyes and thus lowering intraocular pressure.<ref name="AC" /><ref name="Dinnendahl" />

Other PGF<sub>2α</sub> analogues with the same mechanism include [[latanoprost]] and [[travoprost]].<ref name="AC" />

===Pharmacokinetics===
Tafluprost, as a [[lipophilic]] [[ester]], easily penetrates the [[cornea]] and is then activated to the [[carboxylic acid]], tafluprost acid. Onset of action is 2 to 4 hours after application, the maximal effect is reached after 12 hours, and ocular pressure remains lowered for at least 24 hours.<ref name="AC" /><ref name="Dinnendahl" />

Tafluprost acid is inactivated by [[beta oxidation]] to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its [[lactone]], which are subsequently [[glucuronidated]] or [[hydroxylated]]. The [[cytochrome P450]] liver enzymes play no role in the metabolism.<ref name="Dinnendahl" />

An analogous pathway (at least up to the tetranor-metabolites) has been found for latanoprost and travoprost.

[[File:Tafluprost metabolism.svg|thumb|left|upright=3|'''Metabolism'''. From left to right: tafluprost, tafluprost acid (the [[active metabolite]]), 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, 1,2,3,4-tetranortafluprost acid lactone<ref name="Fukano09" /><ref name="Fukano11" />]]
[[File:TAPCOM combination ophthalmic solution.jpg|thumb|A tafluprost/[[timolol]] combination ophthalmic solution]]
{{clear left}}

== References ==
⚫
{{Reflist|32em|refs=

<ref name="PPA">Tafluprost {{drugs.com|PPA|tafluprost}}.</ref>

<ref name="AC">{{cite book|title=Austria-Codex| veditors = Haberfeld H |publisher=Österreichischer Apothekerverlag | location=Vienna |year=2015 |language=German}}</ref>

<ref name="Dinnendahl">{{cite book |title= Arzneistoff-Profile| veditors = Dinnendahl V, Fricke U |publisher=Govi Pharmazeutischer Verlag |location=Eschborn, Germany |date=2011 |edition=25 |volume=9|isbn=978-3-7741-9846-3 |language=German}}</ref>

<ref name="Fukano09">{{cite journal | vauthors = Fukano Y, Kawazu K | title = Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats | journal = Drug Metabolism and Disposition | volume = 37 | issue = 8 | pages = 1622–34 | date = August 2009 | pmid = 19477946 | doi = 10.1124/dmd.108.024885 | s2cid = 12425702 }}</ref>

<ref name="Fukano11">{{cite journal | vauthors = Fukano Y, Kawazu K, Akaishi T, Bezwada P, Pellinen P | title = Metabolism and ocular tissue distribution of an antiglaucoma prostanoid, tafluprost, after ocular instillation to monkeys | journal = Journal of Ocular Pharmacology and Therapeutics | volume = 27 | issue = 3 | pages = 251–9 | date = June 2011 | pmid = 21491995 | doi = 10.1089/jop.2010.0178 }}</ref>

}}


{{Prostaglandins}}
{{Prostaglandins}}
Line 58: Line 98:


[[Category:Prostaglandins]]
[[Category:Prostaglandins]]
[[Category:Secondary alcohols]]

[[Category:Alkene derivatives]]

[[Category:Drugs developed by Merck & Co.]]
{{pharma-stub}}
[[Category:Carboxylate esters]]
4. Sethi HS, Dhawan M, Naik MP, Gupta VS. Prostaglandin analogs in glaucoma. Astrocyte 2015;2:126-32.
[[Category:Isopropyl esters]]
[[Category:Organofluorides]]
[[Category:Phenol ethers]]
[[Category:Ophthalmology drugs]]

Latest revision as of 06:04, 6 April 2024

Tafluprost
Clinical data
Trade namesSaflutan, Taflotan, Zioptan
AHFS/Drugs.comMultum Consumer Information
Routes of
administration		Topical eye drops
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismActivation by ester hydrolysis, deactivation by beta oxidation
Onset of action2–4 hrs
Duration of action≥ 24 hrs
Identifiers
  • Isopropyl (5Z)-7-{(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl}hept-5-enoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.207.745 Edit this at Wikidata
Chemical and physical data
FormulaC25H34F2O5
Molar mass452.539 g·mol−1
3D model (JSmol)
  • CC(C)OC(=O)CCC\C=C/CC(C(O)CC1O)C1\C=C\C(F)(F)COc2ccccc2
  • 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
  • Key:WSNODXPBBALQOF-VEJSHDCNSA-N

Tafluprost (trade names Taflotan by Santen Pharmaceutical, Zioptan by Merck in the US and Saflutan by Mundipharma in Australia) is a prostaglandin analogue. It is used topically (as eye drops) to control the progression of open-angle glaucoma and in the management of ocular hypertension, alone or in combination with other medication. It reduces intraocular pressure by increasing the outflow of aqueous fluid from the eyes.[2][3]

Adverse effects[edit]

The most common side effect is conjunctival hyperemia, which occurs in 4 to 20% of patients. Less common side effects include stinging of the eyes, headache, and respiratory infections. Rare side effects are dyspnoea (breathing difficulties), worsening of asthma, and macular oedema.[2][3][4]

Interactions[edit]

Nonsteroidal anti-inflammatory drugs (NSAIDs) can either reduce or increase the effect of tafluprost.[2] Timolol eye drops, a common kind of glaucoma medication, does not negatively interact with this drug.[3]

No interactions with systemic (for example, oral) drugs are expected because tafluprost does not reach relevant concentrations in the bloodstream.[3][4]

Pharmacology[edit]

Mechanism of action[edit]

Tafluprost is a prodrug of the active substance, tafluprost acid, a structural and functional analogue of prostaglandin F2α (PGF2α). Tafluprost acid is a selective agonist at the prostaglandin F receptor, increasing outflow of aqueous fluid from the eyes and thus lowering intraocular pressure.[3][4]

Other PGF2α analogues with the same mechanism include latanoprost and travoprost.[3]

Pharmacokinetics[edit]

Tafluprost, as a lipophilic ester, easily penetrates the cornea and is then activated to the carboxylic acid, tafluprost acid. Onset of action is 2 to 4 hours after application, the maximal effect is reached after 12 hours, and ocular pressure remains lowered for at least 24 hours.[3][4]

Tafluprost acid is inactivated by beta oxidation to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its lactone, which are subsequently glucuronidated or hydroxylated. The cytochrome P450 liver enzymes play no role in the metabolism.[4]

An analogous pathway (at least up to the tetranor-metabolites) has been found for latanoprost and travoprost.

Metabolism. From left to right: tafluprost, tafluprost acid (the active metabolite), 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, 1,2,3,4-tetranortafluprost acid lactone[5][6]
A tafluprost/timolol combination ophthalmic solution

References[edit]

  1. ^ "Product monograph" (PDF). hres.ca. Retrieved 6 April 2024.
  2. ^ a b c Tafluprost Professional Drug Facts.
  3. ^ a b c d e f g Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  4. ^ a b c d e Dinnendahl V, Fricke U, eds. (2011). Arzneistoff-Profile (in German). Vol. 9 (25 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  5. ^ Fukano Y, Kawazu K (August 2009). "Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats". Drug Metabolism and Disposition. 37 (8): 1622–34. doi:10.1124/dmd.108.024885. PMID 19477946. S2CID 12425702.
  6. ^ Fukano Y, Kawazu K, Akaishi T, Bezwada P, Pellinen P (June 2011). "Metabolism and ocular tissue distribution of an antiglaucoma prostanoid, tafluprost, after ocular instillation to monkeys". Journal of Ocular Pharmacology and Therapeutics. 27 (3): 251–9. doi:10.1089/jop.2010.0178. PMID 21491995.
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