Tafluprost

Last updated
Tafluprost
Tafluprost structure.svg
Clinical data
Trade names Saflutan, Taflotan, Zioptan
AHFS/Drugs.com Multum Consumer Information
Routes of
administration
Topical eye drops
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Activation by ester hydrolysis, deactivation by beta oxidation
Onset of action 2–4 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 InfoCard 100.207.745 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C25H34F2O5
Molar mass 452.539 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]

Contents

Adverse effects

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

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

Mechanism of action

Tafluprost is a prodrug of the active substance, tafluprost acid, a structural and functional analogue of prostaglandin F (PGF). 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 PGF analogues with the same mechanism include latanoprost and travoprost. [3]

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. [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 Tafluprost metabolism.svg
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
A tafluprost/timolol combination ophthalmic solution TAPCOM combination ophthalmic solution.jpg
A tafluprost/timolol combination ophthalmic solution

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<span class="mw-page-title-main">Intraocular pressure</span> Fluid pressure inside the eye

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<span class="mw-page-title-main">Bimatoprost</span> Chemical compound

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<span class="mw-page-title-main">Prostaglandin F2alpha</span> Chemical compound

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Pseudoexfoliation syndrome, often abbreviated as PEX and sometimes as PES or PXS, is an aging-related systemic disease manifesting itself primarily in the eyes which is characterized by the accumulation of microscopic granular amyloid-like protein fibers. Its cause is unknown, although there is speculation that there may be a genetic basis. It is more prevalent in women than men, and in persons past the age of seventy. Its prevalence in different human populations varies; for example, it is prevalent in Scandinavia. The buildup of protein clumps can block normal drainage of the eye fluid called the aqueous humor and can cause, in turn, a buildup of pressure leading to glaucoma and loss of vision. As worldwide populations become older because of shifts in demography, PEX may become a matter of greater concern.

<span class="mw-page-title-main">Netarsudil</span> Chemical compound

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<span class="mw-page-title-main">Secondary glaucoma</span>

Secondary glaucoma is a collection of progressive optic nerve disorders associated with a rise in intraocular pressure (IOP) which results in the loss of vision. In clinical settings, it is defined as the occurrence of IOP above 21 mmHg requiring the prescription of IOP-managing drugs. It can be broadly divided into two subtypes: secondary open-angle glaucoma and secondary angle-closure glaucoma, depending on the closure of the angle between the cornea and the iris. Principal causes of secondary glaucoma include optic nerve trauma or damage, eye disease, surgery, neovascularization, tumours and use of steroid and sulfa drugs. Risk factors for secondary glaucoma include uveitis, cataract surgery and also intraocular tumours. Common treatments are designed according to the type and the underlying causative condition, in addition to the consequent rise in IOP. These include drug therapy, the use of miotics, surgery or laser therapy.

References

  1. https://pdf.hres.ca/dpd_pm/00058012.PDF [ bare URL PDF ]
  2. 1 2 3 Tafluprost Professional Drug Facts .
  3. 1 2 3 4 5 6 7 Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  4. 1 2 3 4 5 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.