Travoprost (DB00287): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Travoprost is a potent and highly selective synthetic prostaglandin F2α (PGF2α​) analogue that has become a cornerstone in the management of elevated intraocular pressure (IOP) associated with open-angle glaucoma (OAG) and ocular hypertension (OHT). As a small molecule therapeutic agent, its primary mechanism of action involves functioning as a full agonist at the prostaglandin F (FP) receptor. This interaction facilitates a significant increase in the outflow of aqueous humor, primarily through the uveoscleral pathway and secondarily through the trabecular meshwork, leading to a robust and sustained reduction in IOP.

Administered as an isopropyl ester prodrug, travoprost is rapidly hydrolyzed by corneal esterases into its active free acid form, a design that enhances corneal penetration while ensuring the active moiety is delivered to the target tissues. Its pharmacokinetic profile is characterized by potent local activity coupled with minimal systemic exposure, rapid systemic metabolism into inactive compounds, and a short plasma half-life, which collectively contribute to a favorable safety profile with predominantly localized adverse effects.

The clinical development of travoprost illustrates a significant evolution in ophthalmic drug delivery, aimed at improving both tolerability and patient adherence. The journey began with the benzalkonium chloride (BAK)-preserved ophthalmic solution (Travatan®), progressed to a formulation with a gentler preservative system (Travatan Z®) to mitigate ocular surface disease, and has most recently culminated in a paradigm-shifting, sustained-release intracameral implant (iDose® TR). This implant, approved by the U.S. Food and Drug Administration (FDA) in 2023, addresses the critical challenge of patient non-adherence by providing continuous drug delivery for an extended period.