Tear concentrations of levofloxacin following topical administration of a single dose of 0.5% levofloxacin ophthalmic solution in healthy volunteers.
BACKGROUND
Several fluorinated carboxyquinolones are used to treat ocular infectious disease. Levofloxacin, in particular, has demonstrated activity against both gram-negative and gram-positive bacteria.


OBJECTIVE
An open-label study was undertaken to assess the pharmacokinetics and ocular bioavailability of levofloxacin in human tears, and to determine the tear concentration of levofloxacin in healthy volunteers, following topical administration of a single-dose of 0.5% levofloxacin ophthalmic solution.


METHODS
Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had > 1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography.


RESULTS
Thirty volunteers were enrolled, with 6 assigned to each of the 5 sampling groups. At 5 minutes after administration of a single topical dose of levofloxacin, the mean tear concentration was 49.19 +/- 26.73 microg/mL. The mean peak concentration of levofloxacin in the tear film, 221.06 +/- 256.68 microg/mL, was reached at 15 minutes after administration. At 4 hours after administration, the mean tear concentration of levofloxacin was 17.04 +/- 15.13 microg/mL. At 6 hours after administration, the mean concentration of levofloxacin was 6.57 +/- 5.26 microg/mL. At 24 hours after administration, levofloxacin concentrations > 2 microg/mL were measured in 2 of 6 (33%) subjects.


CONCLUSIONS
Levofloxacin concentrations in the tear fluid after a single topical dose (1 drop) reached high levels quickly and remained above the minimum inhibitory concentration for most suspected ophthalmic pathogens (< or = 2 microg/mL) for at least 6 hours in most healthy volunteers, and for up to 24 hours in some volunteers.
Raizman
Michael B
MB
Ophthalmic Consultants of Boston, Massachusetts, USA. mraiz@attbi.com
Rubin
Jay M
JM
Graves
Adrienne L
AL
Rinehart
Michael
M
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000493:pharmacokinetics*; D011934:Reagent Strips; D013666:Tears / Q000378:metabolism*; D013997:Time Factors
D000890:Anti-Infective Agents; D009883:Ophthalmic Solutions; D011934:Reagent Strips; D064704:Levofloxacin; D015242:Ofloxacin