Tafluprost

Tafluprost (trade names Taflotan by Santen Pharmaceutical and Zioptan by Merck in the US) 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.[1][2]

Tafluprost
Clinical data
Trade namesSaflutan, Taflotan, Tapros, Zioptan
AHFS/Drugs.comMultum Consumer Information
Pregnancy
category
  • US: C (Risk not ruled out)
    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
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard100.207.745
    Chemical and physical data
    FormulaC25H34F2O5
    Molar mass452.531266 g/mol g·mol−1
    3D model (JSmol)

    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.[1][2][3]

    Interactions

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can either reduce or increase the effect of tafluprost.[1] Timolol eye drops, a common kind of glaucoma medication, does not negatively interact with this drug.[2]

    No interactions with systemic (for example, oral) drugs are expected because tafluprost does not reach relevant concentrations in the bloodstream.[2][3]

    Pharmacology

    Mechanism of action

    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.[2][3]

    Other PGF2α analogues with the same mechanism include latanoprost and travoprost.[2]

    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.[2][3]

    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.[3]

    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[4][5]
    A tafluprost/timolol combination ophthalmic solution

    References
    1. Tafluprost Professional Drug Facts.
    2. Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
    3. Dinnendahl, V; Fricke, U, eds. (2011). Arzneistoff-Profile (in German). 9 (25 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
    4. Fukano, Y; Kawazu, K (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.
    5. Fukano, Y; Kawazu, K; Akaishi, T; Bezwada, P; Pellinen, P (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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