Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.
OBJECTIVE
To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty.


METHODS
In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups.


RESULTS
The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P < 0.05). The endothelial Cmax was 76.1 versus 7.3 microg/g (P > 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P < 0.05). The aqueous Cmax was 0.9 versus 0.3 microg/mL (P > 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups.


CONCLUSIONS
Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.
Holland
Edward J
EJ
Cincinnati Eye Institute, Edgewood, KY, USA. eholland@fuse.net
Lane
Stephen S
SS
Kim
Terry
T
Raizman
Michael
M
Dunn
Steven
S
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077734:Gatifloxacin; D006801:Humans; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014945:Wound Healing
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D011804:Quinolines; D000077734:Gatifloxacin; D000077266:Moxifloxacin