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N.C. Scotty, T.J. Evans, P.J. Johnson, E.A. Giuliano, G. Rottinghaus, A.W. Fothergill, T.J. Cutler, D.E. Brooks; Lufenuron as a Treatment for Equine Keratomycosis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):114.
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Purpose: Lufenuron is a benzoylphenyl urea derivative reported to inhibit chitin synthesis, deposition and polymerization. Based on reports of antifungal efficacy against small animal dermatomycoses, lufenuron is currently being utilized as a treatment for equine keratomycosis. Hypothesis1: Lufenuron inhibits Aspergillus growth in vitro. Hypothesis2: Lufenuron is absorbed into circulation following oral administration in horses in a dose–dependent manner. Methods: Aspergillus isolated from diseased equine corneas were tested in vitro against lufenuron solutions ranging in concentration up to 64 µg/mL. Twenty–one healthy adult horses were divided into 3 treatment groups. Groups 1 and 2 received lufenuron orally at doses of 5 mg/kg and 20 mg/kg, respectively, q 24 h for 3 days. Group 3 received lufenuron orally at a dose of 60 mg/kg, q 24 h for 1 day. Blood samples were collected at hours 0, 1, 2, 3, 6, 12, 24, 48, 72 and 96 after the first dose of lufenuron. Whole blood lufenuron concentrations were determined via HPLC. Data were analyzed using repeated measurement split–plot in time and ANOVA. Mean differences were determined using Fischer’s Least Significant Difference. Statistical significance was set at p<0.05. Results: Lufenuron showed no effect on the growth of Aspergillus in vitro. Lufenuron was detected in the blood of 20 of 21 horses. A dose–dependent relationship was identified in groups 1 and 2, with mean peak lufenuron concentrations of 18.73 ± 4.44 µg/l and 83.47 ± 24.00 µg/l at 72 hours, respectively. The mean peak lufenuron concentration of group 3 was 43.58 ± 9.81 µg/l at hour 6. The mean 24–hour AUCs for groups 2 and 3 did not differ significantly from one another. Conclusions: Lufenuron does not inhibit the growth of equine corneal isolates of Aspergillus in vitro at the doses tested. Lufenuron is absorbed into circulation following oral administration in horses in a dose–dependent manner, and appears to reach saturation after a single dose of 20 mg/kg during the first 24 hours. Significant variability exists between the absorptive capacity of individual horses for lufenuron. Studies providing evidence of lufenuron's efficacy against target fungal species and the accumulation of sufficient concentrations of lufenuron in target tissues are indicated to scientifically justify its use as an antifungal agent in horses.
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