The effect of long-term use and inflammation on the ocular penetration of topical ofloxacin

Purpose. To study the,penetration of ofloxacin into the aqueous and vitreou s humors after long-term topical administration and to investigate the effe cts of inflammation on drug penetration in rabbits. Methods. A standardized model of intraocular infection after penetrating in jury was achieved in the right eyes of 16 rabbits. The animals were randoml y and equally-divided into two groups. The intact left eyes of the groups w ere maintained as the control. Ofloxacin eyedrops (0.3%) were instilled int o all eyes at a frequency of 2 drops every hour for 7 hours in the first gr oup and for 14 hours in the second group. Half an hour after the last drop, samples of the aqueous and vitreous humors were taken and ofloxacin concen trations were measured by using HPLC. Results. The mean aqueous humor concentrations of ofloxacin in control eyes after 7:and 14 hours of instillation were: 1.45 +/- 0.93 mu g/ml and 2.48 +/- 0.33 mu g/ml, respectively; those in infected eyes 2.35 +/- 1.84 mu g/m l and 3.49 +/- 1.47 mu g/ml, respectively. However the differences among th e groups were not significant (p > 0.05). The vitreous ofloxacin concentrat ions in the control eyes were similar after 7 and 14 hours of instillation (0.23 +/- 0.14 mu g/ml, 0.27 +/- 0.10 mu g/ml, respectively). In infected e yes, the mean vitreous ofloxacin concentration after 14 hour of instillatio n was significantly higher than that in control eyes (p < 0.05; 0.4 +/- 0.0 9 mu g/ml, 0.29 +/- 0.11 mu g/ml, respectively). The mean vitreous ofloxaci n concentration in infected eyes after 14 hours instillation was not signif icantly higher than that after 7 hours instillation. Conclusions. Topical ofloxacin instillation for 7 or 14 hours yields aqueou s concentrations above the MIC90 for common ocular pathogens. Prolonged app lication and the presence of inflammation increased the penetration of oflo xacin into the vitreous humor.