Travoprost

Absorption

Travoprost is systemically absorbed through the cornea . In humans, peak plasma concentrations of travoprost free acid were low (25 pg/mL or less) and occurred within 30 minutes following topical ocular administration of one drop of 0.004% travoprost ophthalmic solution .

Toxicity

No cases of overdose have been reported for travoprost . A topical overdose is not likely to occur or to be associated with toxicity . A topical overdose of travoprost may be flushed from the eye(s) with lukewarm water . Treatment of a suspected oral ingestion is symptomatic and supportive .
Travoprost has harmful pharmacological effects on pregnancy and/or the fetus/new-born child. Travoprost should not be used during pregnancy unless clearly necessary . The medication subsequently must not be used in women of childbearing age/potential unless adequate contraceptive measures are in place .
It is unknown whether travoprost from the eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk . The use of travoprost by breast-feeding mothers is not recommended .
There are no data on the effects of TRAVATAN on human fertility . Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose .
Use in patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use .
No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients .
Travoprost has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min) . No dosage adjustment is necessary for these patients .

Description

Travoprost was launched in the US as Travatan?, an ophthalmic solution (0.004%) administered topically for the treatment of elevated intraocular hypertension (lOP) through open-angle glaucoma, a common optic neuropathy and a leading cause of blindness. Travoprost is the isopropyl ester of (+)-fluprostenol, a new prostaglandin derivative belonging to the PGF_2α, analog class. This compound can be prepared in 8 steps from a bicyclic lactone aldehyde by a Wittig alkylidenation followed, after 2 ketonic reductions, by a lactol opening to prostenoic acid while protecting and deprotecting appropriately. Travoprost is a full agonist of FP receptors with a greater affinity than PGF_2α, (K₁ = 52 nM). Pharmacologic studies in rabbits treated daily for a week demonstrated a significant increase of the microvascular optic nerve head blood flow without significant alterations in the systemic flow. In several placebo-controlled clinical studies with hundreds of patients suffering from open-angle glaucoma or ocular hypertension, travoprost (1 to 4 pm daily) dose-dependently reduced lOP (by about 30% at 4 pm); it was shown equal or superior to latanoprost, another prostaglandin analog (5 pm daily) or the adrenergic ~-blocker timolol (500 pm bid). In addition, travoprost was safe and well tolerated with a low incidence of conjunctival hyperaemia.

Chemical properties

Colorless Oil

Originator

Alcon (US)

The Uses of Travoprost

treatment conditions arising from excess uric acid, eg chronic gout

The Uses of Travoprost

Travoprost is a selective FP prostaglandin receptor agonist used to treat glaucoma (1,2).

The Uses of Travoprost

Selective FP prostaglandin receptor agonist. Isopropyl ester of (+)-fluprostenol. Antiglaucoma

What are the applications of Application

15(S)-Fluprostenol isopropyl ester is an unnatural C-15 epimer of Travoprost

Definition

ChEBI: The isopropyl ester of prostaglandin F2alpha in which the pentyl group is replaced by a 3-(trifluoromethyl)phenoxymethyl group. A synthetic analogue of prostaglandin F2alpha, ophth lmic solutions of travoprost are used as a topical medication for controlling the progression of open-angle glaucoma and ocular hypertension, by reducing intraocular pressure. It is a pro-drug; the isopropyl ester group is hydrolysed by esterases in the co nea to the biologically active free acid, fluprostenol.

Background

Travoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure . It is a synthetic prostaglandin F2alpha analog . Having been a well-received therapeutic agent with demonstrated efficacy and safety, travoprost is currently approved by the US FDA as a first-line treatment for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypotension . Furthermore, this approval also solidifies the medication as the first and only prostaglandin analog approved by the FDA for first-line treatment of glaucoma patients that does not contain the preservative benzalkonium chloride . Moreover, travoprost is also currently approved in the EU for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma .

What are the applications of Application

Fluprostenol isopropyl ester is a prodrug PGF2αR agonist

Indications

Travoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension .
Travoprost is also currently indicated for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma .

brand name

Travatan

General Description

Travoprost (Travatan and Travatan-Z) is supplied asa 2.5- or 5.0-mL sterile 0.004% ophthalmic solution in a4.0- or 7.5-mL size container. Travoprost is claimed to bethe most potent and FP-specific analog in this product category. Cautions and side effects are similar to those givenpreviously.

Pharmacokinetics

Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analog that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid . The travoprost free acid is potent and highly selective for the FP prostanoid receptor .

Metabolism

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid . Systemically, travoprost free acid is rapidly and extensively metabolized in the kidney, liver, and lung to inactive metabolites via beta-oxidation of the α(carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14 double bond .