Eye drops and eye gels of levofloxacin: comparison of ocular absorption characterizations and therapeutic effects in the treatment of bacterial keratitis in rabbits

Abstract

The aim was to reveal the characteristic profiles of the marketed levofloxacin eye drops (5 mg/ml) and levofloxacin eye gel (3 mg/g) from the pharmacokinetics and pharmacodynamics views of rabbits’ eyes. A mild and a heavy bacterial keratitis models in rabbits were established. Different regimens of levofloxacin eye drops and eye gel, including phosphate buffer solution (the PBS group), the 4-Sol + 1-Gel group (rabbits were treated with 4 doses of levofloxacin eye drops and 1 dose levofloxacin eye gel per day), the 3-Sol + 1-Gel group (3 doses drops and 1 dose gel), the 4-Sol group (4 doses drops), the 4-Gel group (4 doses gel), the 3-Sol group (3 doses drops), and the 3-Gel group (3 doses gel), were applied to evaluate their efficacies. The ocular pharmacokinetics of levofloxacin eye drops and gel were also investigated. The results of mild infection groups showed that all treatment regimens significantly relieved the infection symptoms, and the treatment effect followed this order: 4-Gel > 4-Sol + 1-Gel > 3-Sol + 1-Gel > 4-Sol > 3-Gel > 3-Sol. In the heavy infection groups, all the treatment regimens significantly relieved the infection symptoms, and the treatment effect also followed the order with the mild infection results. All treatment regimens lowered the number of corneal colony forming units (CFU). Levofloxacin eye gel significantly increased intraocular penetration in rabbits’ eyes. It can be concluded that the levofloxacin eye gel was more effective in treating bacterial keratitis than the levofloxacin eye drops in rabbit keratitis model with a proper treatment regimen such as 4-Gel.

Keywords:

• Levofloxacin
• eye drops
• eye gel
• Staphylococcus aureus
• keratitis
• ocular absorption

Author contributions

X.W. designed the research, G.L., L.X., and M.J. performed the experiments, G.L. and X.W. analyzed data, X.W. and M.J. participated in the discussion. X.W. wrote and revised the paper. All authors reviewed the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China [Project no. 81770895], China Shandong Provincial Key Research and Development Program [SPKR&DP, project no. 2019GSF108027], and the Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering [project no. XTCXQN19].