Tear concentration and safety of levofloxacin ophthalmic solution 1.5% compared
with ofloxacin ophthalmic solution 0.3% after topical administration in healthy
adult volunteers.
Author(s): Walters T, Rinehart M, Krebs W, Holdbrook M.
Affiliation(s): Keystone Research, Ltd., Austin, TX, USA. twalters@austin.rr.com
Publication date & source: 2010, Cornea. , 29(3):263-8
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 microg/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 microg.h/mL and 414.1
+/- 1179.00 microg.h/mL with ofloxacin 0.3%. Maximal concentrations were 806.9
+/- 8.57 and 73.3 +/- 165.46 microg/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.
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