Ocular Biodistribution of Once-Daily 0.6% Bilastine Eye Drops Reveals Highest Levels in Conjunctiva Up to 24 h Postadministration

Abstract

Purpose: Bilastine is a second-generation antihistamine that has been shown to be effective for treatment of allergic conjunctivitis. The objective of this study was to evaluate the pharmacokinetics (PKs) and biodistribution of 0.6% bilastine preservative-free eye drops. Methods: Bilastine was quantified in the conjunctiva, cornea, aqueous humor, vitreous humor, iris/ciliary body, retina/choroid, crystalline lens, and plasma, following a single topical administration to male Dutch-belted rabbits. Results: Concentrations of bilastine were highest in the conjunctiva [C max : 2,545.04 ng/g, at 6 h postadministration; area under the concentration–time curve (AUC t ): 11,382.40 ng·h/g] and cornea (C max : 609.11 ng/g, at 1 h postadministration; AUC t : 1,993.88 ng·h/g), followed by the iris/ciliary body, retina/choroid, aqueous humor, plasma, vitreous humor, and crystalline lens. Quantifiable bilastine concentrations were observed up to 24 h after instillation in the conjunctiva (388.45 ng/g), cornea (28.68 ng/g), iris/ciliary body (12.42 ng/g), retina/choroid (1.91 ng/g), and crystalline lens (0.12 ng/g). In plasma, aqueous humor, and vitreous humor, bilastine was detected up to 12 h postadministration (0.18 ng/mL, 0.40 ng/mL, and 0.32 ng/g, respectively). Conclusions: PKs and biodistribution of 0.6% bilastine eye drops in rabbits revealed a marked preferential distribution in the conjunctiva (target tissue), with sustained levels up to 24 h. These findings are consistent with clinical efficacy trials supporting once-daily administration of topical bilastine for treatment of allergic conjunctivitis.

An emerging antihistamine drug with multiple therapeutic benefits: Bilastine

“…The median time for maximum plasma concentration attained within 2.5 hrs and half-life in plasma has been reported as 7.88 ± 6.72 hrs 14 . However, a recent experiment on a rabbit model for biodistribution of 0.6% bilastine eye drops showed quantifiable concentrations of bilastine up to 24 hrs in the conjunctiva tissues after installation into the eyes 15 . Currently, tablet, solution, buccal, and oral disintegration tablet formulations of bilastine are in clinical use, and other routes of administration and bioavailability are yet to be established through clinical trials.…”

“…In-vitro preclinical studies evidenced that bilastine has specific H1 AH receptor activity and poor or no affinity for other histamine receptors 15 . It has anti-inflammatory effects by preventing human mast cells and degranulocytes from releasing histamine, IL-4, and tumor necrosis factor (TNF) and exhibits anti-inflammatory properties.…”

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions

“…As for the newest bilastine ophthalmic solution, efficacy, tolerability, and efficacy of a once-daily administration have been evaluated in clinical trials to date [31,[35][36][37][38][39]. The bilastine formulation has shown a fast onset of action and efficacy for as long as 16 h post-administration, indicating that it is suitable for a once-daily dosing [31,38]. In a phase three clinical trial, it also showed similar efficacy to a marketed multi-dose formulation of ketotifen 0.025% [35,39].…”

“…This newly EMA-approved bilastine formulation is a preservative-free solution co-formulated with hyaluronic acid, unique in its class, presented in a special multi-dose container. Preclinical in vitro and in vivo studies have shown that these two characteristics (preservative-free with hyaluronic acid) help preserve the tear film and ocular surface integrity [ 31 , 38 ].…”

“…Simplifying dosing can be achieved by prescribing treatments that require once- or twice-daily dosing rather than multiple daily doses [ 69 ]. Once-daily ophthalmic medications are now available for allergic conjunctivitis [ 31 , 37 , 38 ], and this could foster adherence and treatment compliance.…”