title: Tear concentration and safety of levofloxacin ophthalmic solution 1.5% compared with ofloxacin ophthalmic solution 0.3% after topical administration in healthy adult volunteers.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Keystone Research, Ltd., Austin, TX, USA. twalters@austin.rr.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Walters
authors.forename: Mike
authors.initials: M
authors.lastname: Rinehart
authors.forename: William
authors.initials: W
authors.lastname: Krebs
authors.forename: Mark
authors.initials: M
authors.lastname: Holdbrook
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D033401:Microscopy, Acoustic; D008875:Middle Aged; D015242:Ofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000493:pharmacokinetics*; D009887:Ophthalmoscopy; D013666:Tears / Q000378:metabolism*; D014792:Visual Acuity / Q000187:drug effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D064704:Levofloxacin; D015242:Ofloxacin