Penetration of 4th Generation Fluoroquinolones into the Rabbit Aqueous Humor Using a Lidocaine Gel Mixture

Abstract

Abstract: : Purpose: To determine the penetration of 4^th generation fluoroquinolones into the rabbit aqueous humor when administered in a lidocaine gel mixture. Methods: 32 eyes of 16 New Zealand white rabbits were randomized to receive topical gatifloxacin or moxifloxacin mixed in varying concentrations into lidocaine gel. Several different concentrations of antibiotic impregnated gel were created by mixing 5 cc of gel with 1, 2, 4, or 8 drops of antibiotic from the commercial preparations of moxifloxacin 0.5% and gatifloxacin 0.3%. A drop of the chosen mixture was placed into each eye. Approximately 30 minutes following application of the gel, aqueous humor was sampled from all eyes. Fluoroquinolone concentrations in the gel were assayed using HPLC. Results: The majority of the samples obtained had no detectable level of antibiotic in the aqueous. Of the eyes dosed with gatifloxacin–lidocaine gel, 1 of 32 samples had detectable antibiotic at a level of 0.31 µg/ml. Of the eyes dosed with moxifloxacin–lidocaine gel, 7 of 31 aqueous samples had detectable antibiotic at a mean level of .22 µg/ml (n = 7, range .17 – .40 µg/ml). All of the samples for both antibiotics that had a detectable level in the aqueous were mixtures of 8 drops of antibiotic to 5 cc of lidocaine gel. This difference between the numbers of detectable samples for each antibiotic was statistically significant (P = .0168). The level of detection of the HPLC assay was 0.08 µg/ml. Conclusions: A topical mixture of lidocaine gel and 4^th generation fluoroquinolones failed to produce detectable quantities of antibiotic in the aqueous humor in 3 of the 4 different concentration mixtures used. The 8 drops of antibiotic to 5 cc of gel mixture produced detectable levels in 1 of 8 gatifloxacin samples and 7 of 8 moxifloxacin samples. These levels were above the reported MIC_90s for some, but not all pathogens of concern. Higher aqueous levels can be generated by direct topical application of the antibiotics. Improved aqueous levels may be obtained by creating more concentrated antibiotic–gel mixtures, and may represent a practical method for pre–operative dosing for topical cataract surgery.

Keywords: aqueous • pharmacology • antibiotics/antifungals/antiparasitics