Ocular pharmacokinetics of a new preservative‐free bimatoprost 0.01% ophthalmic gel

Abstract

Aims/Purpose: The aim of this study was to compare the aqueous humour (AH) and iris‐ciliary body (ICB) concentrations of bimatoprost and its main metabolite bimatoprost free acid after topical instillation in rabbits of a new preservative‐free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) versus two commercially available preserved bimatoprost ophthalmic solutions ‐ PB 0.01% (200 ppm benzalkonium chloride [BAK], Lumigan® 0.01%) and PB 0.03% (50 ppm BAK, Lumigan® 0.03%).Methods: Female Dutch Belted rabbits (n = 45) were divided into three treatment groups (30 eyes per group): PFB 0.01% gel, PB 0.01% and PB 0.03% solutions. Animals received a single topical instillation (25 μL) into both eyes. AH and ICB samples were collected at 0.5 h, 1 h, 2 h, 4 h and 8 h post instillation. These samples were analysed by rapid resolution liquid chromatography tandem mass spectrometry for bimatoprost and bimatoprost free acid concentrations.Results: Following a single topical instillation, Tmax of bimatoprost and bimatoprost free acid in both ocular matrices was 1 h across the 3 treatments. Cmax of bimatoprost/bimatoprost free acid was 50.2 ng/mL, 26.3 ng/mL and 59.9 ng/mL of AH respectively following PFB 0.01%, PB 0.01% and PB 0.03% treatments. Maximal concentrations and area under the curve in AH and ICB of bimatoprost/bimatoprost free acid were greater (from 2‐ to 2.6‐fold) with PFB 0.01% gel compared to PB 0.01% and similar (from 0.9‐ to 0.95‐fold) to PB 0.03%.Conclusions: Topical instillation of PFB 0.01% gel produced significantly higher bimatoprost/bimatoprost free acid concentrations in the AH and ICB of rabbits than PB 0.01% (despite a high BAK concentration) and was similar to PB 0.03%. The preservative‐free gel formulation improves corneal penetration and bioavailability of bimatoprost compared to a preserved solution at the same concentration.