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Tear Concentration and Safety of Levofloxacin Ophthalmic Solution 1.5% Compared With Ofloxacin Ophthalmic Solution 0.3% After Topical Administration in Healthy Adult Volunteers

Walters, Thomas MD; Rinehart, Mike BS; Krebs, William PhD; Holdbrook, Mark BA

doi: 10.1097/ICO.0b013e3181b55fce
Clinical Science

Purpose: This study evaluated the tear concentration and safety of levofloxacin ophthalmic solution 1.5%.

Methods: Healthy adult volunteers (N = 125) received a single initial two-drop bilateral dose of either levofloxacin 1.5% (n = 100) or ofloxacin 0.3% (n = 25). Tear-fluid drug concentrations were measured at 15 minutes and at 2, 6, 12, and 24 hours after dosing. Subjects were dosed every 2 hours while awake and 4 and 6 hours after retiring (Days 1-3) and four times daily while awake (Days 4-14). Final measurements and evaluations were done on Day 15. Tear concentrations were determined by high-performance liquid chromatography. Safety and tolerability parameters included visual acuity, ophthalmoscopy, biomicroscopy, rose bengal staining, and adverse effects.

Results: Tear concentrations after a single two-drop dose of levofloxacin 1.5% and ofloxacin 0.3% were above 2 μg/mL, a concentration that exceeds the minimum inhibitory concentration90 for levofloxacin in typical ocular bacterial pathogens at all time points through 24 hours. The area under the curve for the first 12 hours for levofloxacin 1.5% was 2703.5 ± 574.22 μg·h/mL and 414.1 ± 1179.00 μg·h/mL with ofloxacin 0.3%. Maximal concentrations were 806.9 ± 8.57 and 73.3 ± 165.46 μg/mL, respectively. Levofloxacin 1.5% and ofloxacin 0.3% did not differ in adverse event incidence, except for transient mild/moderate dysgeusia (14% of levofloxacin-treated subjects versus 4% of ofloxacin-treated subjects). No corneal epithelial damage or inflammatory changes were associated with levofloxacin.

Conclusion: A single dose of levofloxacin 1.5% produced tear fluid concentrations that were well above the minimum inhibitory concentration90 for typical ocular pathogens and was safe and well tolerated.

From the *Keystone Research, Ltd., Austin, TX; and †Santen Inc., Napa, CA.

Received for publication September 5, 2008; revision received June 23, 2009; accepted June 24, 2009.

Reprints: Thomas Walters, MD, Keystone Research, Ltd., 5717 Balcones Drive, Austin, TX 78731 (e-mail:

Copyright © 2010 Wolters Kluwer Health, Inc. All rights reserved.