Tear Concentration of 1.5% Levofloxacin Ophthalmic Solution Following Topical Administration in Healthy Adult Volunteers

Abstract

Abstract: : Purpose: Prevention or resolution of bacterial ophthalmic infections may best be achieved with antimicrobials that rapidly attain or exceed the MIC₉₀ for common ophthalmic pathogens. The MIC₉₀ for Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pnuemoniae and Pseudomonas aeruginosa with levofloxacin (LVFX) is 0.39, 0.78, 1.56 and 3.13 µg/mL respectively and with ofloxacin (OFLX) is 0.78, 1.56, 3.13 and 6.25 µg/mL respectively. This study measured the concentration in tears of healthy adult volunteers following topical administration of 1.5% LVFX or 0.3% OFLX and monitored the safety and tolerability parameters of both. Methods: A total of 125 healthy adult volunteers with asymptomatic eyes were enrolled in a randomized, parallel-group, double-masked, single-center study. Informed consent was obtained, and subjects were assigned to receive either 1.5% LVFX or 0.3% OFLX (4:1 ratio) administered bilaterally over a 15-day period. On day 0 of the study, subjects received one bilateral dose consisting of two drops. Tear samples were collected at 15 min, 2 hr, 6 hr, 12 hr, and 24 hr (25 subjects at each sampling time) post-administration using Schirmer strips. The quantity of drug was determined by HPLC assay to compute the concentration. Safety and tolerability parameters included visual acuity testing, ophthalmoscopy, biomicroscopy and Rose Bengal staining, and subjects were monitored for adverse effects. Results: LVFX concentration in tears (24.2 µg/mL) was significantly greater (p=0.021) than OFLX (6.9 µg/mL), 12 hours after topical administration, and greater at all timepoints measured. Mean concentrations of both antimicrobials in tear fluid for each sampling time are presented in Table 1. Table 1. Mean concentrations of LVFX and OFLX ophthalmic solutions in tear fluid (µg/mL) after topical administration in healthy adult volunteers. * p = 0.021 Conclusions: 1.5% LVFX rapidly achieved tear-fluid concentration well above the MIC₉₀ for most ophthalmic pathogens and remained above MIC₉₀ at all time points tested after dosing. Both 1.5% LVFX and 0.3% OFLX ophthalmic solutions were well tolerated in this study.  

Keywords: antibiotics/antifungals/antiparasitics • cornea: tears/tear film/dry eye • pharmacology