MRSA Research Today is a free monthly online journal that collates and summarizes the latest research about MRSA, including details on methicillin-resistant staphylococcus aureus, hospitals, infection, antibiotic resistance, superbugs. | ||||||||
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Antibiotic effects of WP-0405, a thermo-setting ofloxacin gel, on methicillin-resistant Staphylococcus aureus keratitis in rabbits.Fukaya Y, Kurita A, Tsuruga H, Naito A, Nakaya S, Sato M, Kamata Y, Hirata H, Kambara Y, Kurasawa N, Wada T, Toyoda Y, Shirasawa E, Ohashi Y Research and Development Division, Wakamoto Pharmaceutical Co., Ltd., Kanagawa, Japan. fukaya@wakamoto-pharm.co.jp PURPOSE: The chemotherapeutic effects and pharmacokinetics properties of WP-0405 (a thermo-setting in situ 0.3% ofloxacin-containing ophthalmic gel) and ofloxacin (a conventional 0.3% ofloxacin solution) on methicillin-resistant Staphylococcus aureus (MRSA) keratitis were compared in a rabbit model. METHOD: The single-instillation pharmacokinetics of WP-0405 and ofloxacin in the cornea, aqueous humor, conjunctiva, and iris-ciliary body were determined in normal rabbit eyes. To compare the duration of antimicrobial action, WP-0405 or ofloxacin was instilled oncedaily in an early-treatment model of keratitis, and corneas were either removed immediately or 4 or 8 h postinstillation. In another experiment, WP-0405 was instilled two or three times daily to compare its antibiotic efficacy with three-times daily instillation of ofloxacin in the same early-treatment model of keratitis; corneas were then removed after determining the extent of the abscess area. In another experiment, WP-0405 was instilled four or eight times daily to compare its effects with eight-times daily instillation of ofloxacin in a late-treatment model of keratitis, and corneas were removed. The number of viable bacteria in the corneas was determined in all experiments. RESULTS: Cmax and AUC0- in tissues treated with WP-0405 were 1.5-3.4-fold and 1.8-2.9-fold greater than those treated with ofloxacin, respectively. WP-0405 significantly reduced the number of viable bacteria for up to 8 h after a single instillation. WP-0405 not only significantly reduced the number of viable bacteria, but also the size of the abscess area at the same frequency of instillation. When compared to ofloxacin, WP-0405 exhibited an approximately equivalent antibiotic effect, with fewer administrations. CONCLUSIONS: As a result of its pharmacokinetics, WP-0405 had a more potent, longer-acting antibiotic effect than did ofloxacin. Furthermore, because of its lower required instillation frequency, which would improve patient compliance, WP-0405 has great potential therapeutic benefits. Published 16 August 2006 in J Ocul Pharmacol Ther, 22(4): 258-66.
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