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Lomefloxacin is known to have an excellent corneal penetration. The therapeutic effect of two specific treatment regimens with lomefloxacin 0.3% eye drops was studied in a Pseudomonas aeruginosa-induced keratitis model in guinea pigs. An initial loading dose of 1 drop every 5 min for 5 times was used in all groups. Its purpose was to obtain high bactericidal corneal levels in the two actively treated groups. The follow-up treatment for 7 days was by a twice daily regimen in one group and 3 times daily in the other treated group. There were two control groups - one with no treatment and the other with vehicle treatment (initial loading dose followed by twice daily regimen). Clinical signs of cornea, conjunctiva and eye adnexae improved significantly within 2 days in both lomefloxacin regimens, whereas clinical signs deteriorated with vehicle treatment. Fifty percent of the animals treated with lomefloxacin showed no colonies in the swab culture after 2 days of therapy, while all vehicle-treated animals were positive even at day 6, with 5 out of 9 animals continuing to be positive at day 8. Pseudomonas in the range of 100-2,300 colonies was isolated from the grounded and cultured cornea at the end of the study in 4 out of 9 vehicle-treated animals but in none of the lomefloxacin-treated guinea pigs. The biggest difference in the degree of secondary inflammation between lomefloxacin and vehicle-treated groups was observed in the cornea which was the target tissue of infection. An unexpected observation was the lower degree of corneal inflammation in the twice daily treated animals when compared to the 3 times daily treatment group. This finding may be due to the somewhat lower initial degree of corneal inflammation in this group and suggests that the course of corneal recovery is predominately dependent on the initial degree of infection with both dosage regimens of lomefloxacin capable of eradicating corneal organisms.