Optimizing topical antibiotic delivery in dogs: Tear film pharmacokinetics of moxifloxacin following pre-treatment with hyaluronic acid
Abstract
Purpose To evaluate the impact of pre-treatment with mucoadhesive polymers on tear film concentrations of topically administered moxifloxacin in dogs. Methods Eight healthy dogs were enrolled in a randomized paired-eye crossover study consisting of two sessions (7-day washout). Eyes received topical 0.5% moxifloxacin alone (control) or following pre-treatment with a mucoadhesive polymer applied 30 seconds earlier: either 0.2% hyaluronic acid (HA; Hylogel ® ) or 0.75% cross-linked hyaluronic acid (XHA; Oculenis ® ). Tear samples were collected using microcapillary tubes at baseline and predefined intervals up to 480 minutes, and moxifloxacin concentrations were quantified by UV-Vis spectrophotometry (293 nm). Results Total moxifloxacin exposure (AUC 0–480 ) increased following pre-treatment with either HA formulation. The XHA produced a statistically significant 2.0-fold increase in mean AUC 0–480 over control (47,929 vs. 24,417 µg·min/mL; P = 0.005). The HA group achieved a 1.8-fold increase in mean AUC 0–480 (37,104 vs. 20,693 µg·min/mL), but this did not reach statistical significance (P = 0.154). In the XHA trial, a significant treatment effect (P = 0.012) and interaction (P = 0.002) were observed for concentration, which remained significantly higher than control for 15 minutes (P ≤ 0.018). In the HA trial, a significant treatment effect was noted for concentration (P = 0.020), with levels remaining significantly higher than control for 10 minutes (P ≤ 0.024). No ocular irritation was observed. Conclusion Prior administration of mucoadhesive polymers increases moxifloxacin bioavailability on the canine ocular surface, with this effect being more pronounced for cross-linked HA (“reservoir effect”) compared to linear HA formulations. These findings may help optimize topical antibiotic delivery strategies in dogs with bacterial keratitis.
Article Details
Authors (5)
Lionel Sebbag
Bar Fruchter
Daphne Kenin
Dikla Arad
Oren Pe’er