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Mechanism of Action
Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.
Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from four multiple dose pharmacokinetic studies (totaling 107 subjects) have shown that plasma concentrations of the free acid are below 0.01 ng/ml (the quantitation limit of the assay) in two-thirds of the subjects. In those individuals with quantifiable plasma concentrations (N=38), the mean plasma Cmax was 0.018 ± 0.007 ng/ml (ranged 0.01 to 0.052 ng/mL) and was reached within 30 minutes. From these studies, travoprost is estimated to have a plasma half-life of 45 minutes. There was no difference in plasma concentrations between Days 1 and 7, indicating steady-state was reached early and that there was no significant accumulation.
Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized 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.
The elimination of travoprost free acid from plasma was rapid and levels were generally below the limit of quantification within one hour after dosing. The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes. Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.
In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 25-27 mm Hg who were treated with TRAVATAN® (travoprost ophthalmic solution) 0.004% dosed once-daily in the evening demonstrated 7-8 mm Hg reductions in intraocular pressure. In subgroup analyses of these studies, mean IOP reduction in black patients was up to 1.8 mm Hg greater than in non-black patients. It is not known at this time whether this difference is attributed to race or to heavily pigmented irides.
In a multi-center, randomized, controlled trial, patients with mean baseline intraocular pressure of 24-26 mm Hg on TIMOPTIC* 0.5% BID who were treated with TRAVATAN® (travoprost ophthalmic solution) 0.004% dosed QD adjunctively to TIMOPTIC* 0.5% BID demonstrated 6-7 mm Hg reductions in intraocular pressure.
Last reviewed on RxList: 9/19/2011
This monograph has been modified to include the generic and brand name in many instances.
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