Absorption and Distribution of Moxifloxacin, Ofloxacin and Gatifloxacin into Ocular Tissues and Plasma Following Topical Ocular Administration to Pigmented Rabbits.

Abstract

Abstract: : Purpose: To measure the ocular absorption and distribution of moxifloxacin, ofloxacin and gatifloxacin following repeated topical ocular doses of VIGAMOX^TM, OCUFLOX^TM or ZYMAR^TM to rabbits. Methods: Male Dutch belted rabbits received a thorough slit–lamp biomicroscopic examination prior to dosing. Only rabbits with no ocular defects were randomized into the three test groups. The eyes of the rabbits were dosed with VIGAMOX, OCUFLOX or ZYMAR three times per day for three days. After the morning dose on the fourth day, aqueous humor, cornea, iris–ciliary body, vitreous humor and plasma were collected at selected time points (3 pairs, or N=6 per time–point) for analyses of drug concentrations by a reverse phase HPLC/fluorescence method. Results: As expected, all three fluoroquinolones were absorbed into the eye. In aqueous humor the maximal concentrations were (mean ± SD): moxifloxacin (1.42 ± 0.61 ug/mL) > ofloxacin (0.405 ± 0.135 ug/mL) > gatifloxacin (0.310 ± 0.75 ug/mL). In cornea the results were: moxifloxacin (24.8 ± 1.3 ug/g) > ofloxacin (8.01 ± 2.8 ug/g) > gatifloxacin (4.85 ± 0.70 ug/g). In vitreous humor the maximal concentrations were moxifloxacin (0.082 ± 0.038 ug/g) > ofloxacin (0.003 ± 0.002 ug/g) and gatifloxacin (0.003 ± 0.004 ug/g). Retention of all three compounds was observed in the pigmented iris–ciliary body due to melanin binding, which is characteristic of fluoroquinolones. Maximal plasma concentrations were about 0.01 ug/mL for all three compounds and declined rapidly. Conclusions: These results show that moxifloxacin is well absorbed into the anterior ocular tissues and vitreous humor. Concentrations achieved are 3– to 4–fold higher than gatifloxacin and ofloxacin.

Keywords: anterior chamber • antibiotics/antifungals/antiparasitics