Ocular biodistribution of once‐daily bilastine eye drops reveals highest levels in conjunctiva up to 24 hours post‐administration

Abstract

AbstractPurposeA novel effective, safe and well tolerated topical formulation of bilastine, a second‐generation H1‐antihistamine, has been developed for allergic conjunctivitis treatment. This in vivo biodistribution study aimed to determine the exposure to topical bilastine of different ocular tissues and verify if the evolution of conjunctival levels over time supports the intended once daily posology.MethodsTwenty‐four Dutch‐Belted rabbits received 30 µl/eye of 6 mg/ml bilastine formulation (a preservative free artificial tear containing sodium hyaluronate). Blood samples were obtained through the ear artery. Three animals were sacrificed per time point, and aqueous and vitreous humor, cornea, conjunctiva, iris/ciliary body, crystalline lens and retina/choroid samples were collected from both eyes. Bilastine concentrations in matrices were determined by validated LC‐MS/MS methods and pharmacokinetic parameters were determined usin a non‐compartmental analysis.ResultsBilastine Cmax was achieved from 30 min to 6 h after drug administration. Bilastine exposure was highest in conjunctiva (Cmax: 2545.04 ng/g, at 6 h post‐administration; AUCt: 11382.40 ng·h/g) and cornea (Cmax: 609.11 ng/g, at 1 h post‐administration; AUCt: 1993.88 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 post‐instillation in 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 and vitreous humor, bilastine was detected up to 12 h post‐administration.ConclusionsThe results show the preferential distribution of bilastine eye drops in the conjunctiva, the intended target tissue, while absorption is limited and potential for systemic side effects low. Significant levels of bilastine found in conjunctiva up to 24 h post‐dose support the once daily posology.