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J.M. Levine, R. Noecker, L. Herrygers, T. Clark; Aqueous Levels of Moxifloxacin and Gatifloxacin Following Different Pre and Post–Operative Topical Dosing Protocols. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4911.
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Purpose: To determine aqueous levels of moxifloxacin and gatifloxacin following different topical dosing protocols. Methods: 40 eyes of 20 New Zealand white rabbits were randomized to receive the commercial preparation of topical gatifloxacin or moxifloxacin following one of two dosing protocols. In the first protocol, the eyes were dosed QID for 4 days to simulate typical pre–operative cataract dosing. 30–60 minutes following the last dose, the aqueous humor was sampled. The anterior chamber then received a "washout" with balanced salt solution for approximately one minute to simulate the irrigation of the anterior chamber during cataract surgery. 30–60 minutes following the washout, the aqueous was re–sampled. In the second protocol, the eyes were dosed QID for 4 days, and then dosed intensively q10 minutes for 4 doses to simulate intensive preoperative cataract dosing. 10 minutes after the last dose, the aqueous was sampled. The anterior chamber then received a "washout" with BSS for approximately one minute. The eyes were then dosed q5 minutes X 4 doses, followed by repeat aqueous sample 5 minutes following the last dose to simulate intensive post–operative dosing. Fluoroquinolone concentration was assayed with HPLC. Results: In the first protocol with typical preoperative QID dosing, the mean level of gatifloxacin was 0.269 µg/ml (n=5, range .182–.312 µg/ml) and of moxifloxacin was 2.111 µg/ml (n=9, range 1.036–4.416 µg/ml) (P=.0035). Following the washout, the mean level of gatifloxacin was 0.229 µg/ml (n=6, range .149 – .352 µg/ml) and of moxifloxacin was .619 µg/ml (n=8, range .361– 1.041 µg/ml) (P=.0007). In the second protocol with q10 minute intensive dosing, the mean level of gatifloxacin was 1.871 µg/ml (n=8, range .929– 3.955 µg/ml) and of moxifloxacin was 4.940 µg/ml (n=9, range 3.21–8.352 µg/ml) (P=.0006). Following aqueous washout and q5 minute dosing, the mean level of gatifloxacin was 1.677 µg/ml (n=8, range .981– 2.468 µg/ml) and of moxifloxacin was 9.470 µg/ml (n=6, range 6.048 –16.863 µg/ml) (P=.00009). Conclusions: The differences in concentrations obtained through these protocols illustrates that care must be taken with design of pre and post–operative antibiotic dosing protocols. While QID dosing achieved levels in excess of the reported MIC90s for methacillin–sensitive S. aureus and Streptococcus sp., gatifloxacin did not achieve levels in excess of the MIC90s for S. epidermidis (2 µg/ml) and methacillin–resistant S. aureus (2–4 µg/ml). Intensive dosing is effective in producing higher pre and post–operative antibiotic levels.
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