Tafluprost (trade names Taflotan by

Santen Pharmaceutical , is a Japanese pharmaceutical company, specializing in ophthalmology. With its ophthalmic products Santen holds the top share within the Japanese market and is one of the leading ophthalmic companies worldwide, with its products being sold in ove ...

, Zioptan by Merck in the US and Saflutan by Mundipharma in Australia) is a

prostaglandin analogue Prostaglandin analogues are a class of drugs that bind to a prostaglandin receptor. Wider use of prostaglandin analogues is limited by unwanted side effects and their abortive potential. Uses Prostaglandin analogues such as misoprostol are use ...

. It is used topically (as

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

s) to control the progression of

open-angle glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

and in the management of

ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and 2 ...

, alone or in combination with other medication. It reduces

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

by increasing the outflow of aqueous fluid from the eyes.

Adverse effects

The most common side effect is

conjunctival hyperemia Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...

, which occurs in 4 to 20% of patients. Less common side effects include stinging of the eyes, headache, and

respiratory infection Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...

s. Rare side effects are

dyspnoea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing dis ...

(breathing difficulties), worsening of

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

, and macular oedema.

Interactions

Nonsteroidal anti-inflammatory drugs (NSAIDs) can either reduce or increase the effect of tafluprost.

Timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest pa ...

eye drops, a common kind of glaucoma medication, does not negatively interact with this drug. No interactions with systemic (for example, oral) drugs are expected because tafluprost does not reach relevant concentrations in the bloodstream.

Pharmacology

Mechanism of action

Tafluprost is a prodrug of the active substance, tafluprost acid, a

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such ...

and functional analogue of prostaglandin F_2α (PGF_2α). Tafluprost acid is a selective agonist at the

prostaglandin F receptor Prostaglandin F receptor (FP) is a receptor belonging to the prostaglandin (PG) group of receptors. FP binds to and mediates the biological actions of Prostaglandin F2α (PGF2α). It is encoded in humans by the ''PTGFR'' gene. Gene The ''PTG ...

, increasing outflow of aqueous fluid from the eyes and thus lowering intraocular pressure. Other PGF_2α analogues with the same mechanism include

latanoprost Latanoprost, sold under the brand name Xalatan among others, is a medication used to treat increased pressure inside the eye. This includes ocular hypertension and open angle glaucoma. It is applied as eye drops to the eyes. Onset of effects i ...

and

travoprost Travoprost, sold under the brand name Travatan among others, is a medication used to treat high pressure inside the eye including glaucoma. Specifically it is used for open angle glaucoma when other agents are not sufficient. It is used as an eye ...

Pharmacokinetics

Tafluprost, as a

lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

, easily penetrates the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

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. Tafluprost acid is inactivated by

beta oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cyc ...

to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

, which are subsequently

glucuronidated Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosid ...

or hydroxylated. The

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

liver enzymes play no role in the metabolism. An analogous pathway (at least up to the tetranor-metabolites) has been found for latanoprost and travoprost. Tafluprost metabolism

References

{{Prostanoidergics Prostaglandins Secondary alcohols Alkene derivatives Merck & Co. brands Carboxylate esters Isopropyl esters Organofluorides Phenol ethers Ophthalmology drugs