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S. Nakaya, A. Kato, Y. Ohyama, M. Sato, T. Wada, H. Hirata, E. Shirasawa, Y. Ohashi; Enhancement and Prolongation of Antibacterial Activity of Ofloxacin Delivery in a Thermo-Setting Gel. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1984.
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© ARVO (1962-2015); The Authors (2016-present)
WP-0405 (a thermo-setting 0.3% ofloxacin-containing ophthalmic gel) is a novel delivery system whose drug residence time on the ocular surface is prolonged relative to that obtained following eyedrop application. To further evaluate WP-0405 attributes, we determined if its antibacterial efficacy is greater and more prolonged than that obtained following eyedrop application of Tarivid (0.3% ofloxacin). Accordingly, we compared the time dependent antibacterial activities of Tarivid and WP-0405 against different methicillin-resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococci (CNS) strains.
An in vitro dynamic model was used that simulates the changes in ofloxacin concentration in the cornea based on measurements of WP-0405 and Tarivid pharmacokinetic profiles resulting from a single drug instillation to rabbit eyes (Y. Fukaya et al. J. Ocul. Pharamcol. Ther., 22: 258, 2006). To determine antibacterial activity, clinical isolates of 5 MRSA and 5 CNS strains were applied to the dynamic model. Time dependent changes in the remaining viable cell population were determined with the agar dilution method at 0, 15, 120, 240, 300, 360, 420 and 480 min. Time dependent changes in ofloxacin concentration were analyzed with HPLC at 0, 5, 15, 30, 60, 120, 180, 240, 360 and 480 min.
When compared to Tarivid, WP-0405 significantly reduced the number of viable MRSA No.5 (MIC: 8 µg/ml) for up to 8 hours in the in vitro dynamic model (p<0.01). Similarly, the antimicrobial activities of WP-0405 against three other MRSA strains (MIC: 2-16 µg/ml) and 5 CNS strains (MIC: 0.25-16 µg/ml) were greater than those of Tarivid. However, both WP-0405 and Tarivid showed no activity against one MRSA strain (MIC: 32 µg/ml).
Based on the results of the dynamic model, WP-0405 is more bactericidal and has a longer- acting antibiotic effect than Tarivid. These differences indicate that ofloxacin has greater antibacterial activity over a longer period when it is released from a thermo setting gel than applied as eyedrops. This model can be used instead of the in vivo keratitis model for comparative evaluation of antimicrobial agents since it is a convenient method and provides meaningful insight into this question.
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