Aqueous humor penetration of topical bimatoprost 0.01% and bimatoprost 0.03% in rabbits

Abayomi B Ogundele, Mark C Jasek
Alcon Research Ltd, Fort Worth, TX, USA

Purpose: The purpose of this study was to compare the aqueous humor concentrations of bimatoprost acid after topical instillation in rabbits of bimatoprost ophthalmic solution 0.01% and bimatoprost ophthalmic solution 0.03%, two commercially available intraocular pressure-lowering medications.
Methods: Male Dutch Belted rabbits were divided into two treatment groups (four rabbits/eight eyes per group): bimatoprost 0.01% and bimatoprost 0.03%. Thirty microliters (µL) of study medication was to pically instilled into both eyes of each animal. Thirty minutes and 90 minutes after instillation, aqueous humor samples were collected. These samples were analyzed by reverse-phase high-performance liquid chromatography for bimatoprost acid concentration.
Results: Following a single topical ocular instillation, the bimatoprost 0.01% formulation had a lower mean aqueous humor concentration of bimatoprost acid than the bimatoprost 0.03% formulation at both 30 minutes (11.5 ± 2.1 ng/mL versus 37.8 ± 28.8 ng/mL; P = 0.17) and 90 minutes (20.8 ± 5.7 ng/mL versus 45.8 ± 14.3 ng/mL; P = 0.03) after topical instillation.
Conclusions: Topical ocular instillation of bimatoprost 0.01% produced significantly lower bimatoprost acid concentration in the aqueous humor of rabbits than bimatoprost 0.03%, despite the 4-fold increase of benzalkonium chloride contained in bimatoprost 0.01%.

Keywords: aqueous humor, benzalkonium chloride, bimatoprost, pharmacokinetics, preclinical, prostaglandin analog