Tafluprost
{{Drugbox | IUPAC_name = Isopropyl (5Z)-7-{(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl}hept-5-enoate | image = Tafluprost_structure.svg
| tradename = Saflutan, Taflotan, Tapros, Zioptan | Drugs.com = Multum Consumer Information | pregnancy_AU = | pregnancy_US = C | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = Rx-only | legal_status = | routes_of_administration = Topical (eye drops)
| bioavailability = | protein_bound = | metabolism = Activation by ester hydrolysis, deactivation by beta oxidation | metabolites = | onset = 2–4 hrs | elimination_half-life = | duration_of_action = ≥ 24 hrs | excretion =
| CAS_number = 209860-87-7
| ATC_prefix = S01
| ATC_suffix = EE05
| ATC_supplemental =
| PubChem = 6433101
| ChEBI_Ref = 
| ChEBI = 66899
| DrugBank = DB08819
| ChEMBL = 1963683
| ChemSpiderID = 8044182
| UNII_Ref =
| UNII = 1O6WQ6T7G3
| KEGG = D06274
| chemical_formula = | 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 | 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 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]
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.
References
- ^ a b c Tafluprost Professional Drug Facts.
- ^ a b c d e f g Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- ^ 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.
- ^ 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.
- ^ 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.