Tafluprost

Tafluprost
Clinical data
Trade names	Saflutan, Taflotan, Tapros, Zioptan
AHFS/Drugs.com	Multum Consumer Information
Routes of; administration	Topical (eye drops)
ATC code	S01EE05 (WHO) ;
Legal status
Legal status	US: ℞-only ;
Pharmacokinetic data
Metabolism	Activation by ester hydrolysis, deactivation by beta oxidation
Onset of action	2–4 hrs
Duration of action	≥ 24 hrs
Identifiers
	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;
CAS Number	209860-87-7;
PubChem CID	6433101;
DrugBank	DB08819;
ChemSpider	8044182;
UNII	1O6WQ6T7G3;
KEGG	D06274;
ChEBI	CHEBI:66899 ;
ChEMBL	ChEMBL1963683;
ECHA InfoCard	100.207.745
Chemical and physical data
Formula	C25H34F2O5
Molar mass	452.539 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)OC(=O)CCC\C=C/CC(C(O)CC1O)C1\C=C\C(F)(F)COc2ccccc2;
	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; Key: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 F_2α (PGF_2α). 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 PGF_2α 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

Tafluprost Professional Drug Facts.
Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
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 (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.
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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[PPA-1] Tafluprost Professional Drug Facts.

[AC-2] Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.

[Dinnendahl-3] 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.

[Fukano09-4] 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.

[Fukano11-5] 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.