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.
