BACKGROUND AND OBJECTIVES: Triturated (crushed and suspended) ketoconazole has been recommended for the treatment of fungal keratitis when commercial antifungal eyedrops are unobtainable. The authors evaluated the in vivo corneal stromal concentration with different vehicles in the eyes of adult rabbits. MATERIALS AND METHODS: Ketoconazole and itraconazole tablets were triturated to 20 mg/ml in four vehicles: polyvinyl alcohol (PVA), boric acid, olive oil, and balanced salt solution (BSS). Six eyes (deepithelialized for better penetration) received one drop every 15 minutes for 2 hours. A yeast overlay bioassay of extracts determined the stromal concentration. RESULTS: Itraconazole in BSS, olive oil, PVA, and boric acid produced inhibition zones of 17.3, 15.6, 15.4, and 13.2 mm, respectively. Ketoconazole produced inhibition zones of 35.9, 39.4, 41.8, and 44.7 mm, respectively. From a standard curve, the concentrations of ketoconazole in tissue were 512, 773, 1221, and 1492 micrograms/g, respectively. CONCLUSION: The vehicle that is used to triturate antifungals affects the tissue concentration. This may have an impact on fungal keratitis therapy.
BACKGROUND AND OBJECTIVES: Triturated (crushed and suspended) ketoconazole has been recommended for the treatment of fungal keratitis when commercial antifungal eyedrops are unobtainable. The authors evaluated the in vivo corneal stromal concentration with different vehicles in the eyes of adult rabbits. MATERIALS AND METHODS:Ketoconazole and itraconazole tablets were triturated to 20 mg/ml in four vehicles: polyvinyl alcohol (PVA), boric acid, olive oil, and balanced salt solution (BSS). Six eyes (deepithelialized for better penetration) received one drop every 15 minutes for 2 hours. A yeast overlay bioassay of extracts determined the stromal concentration. RESULTS:Itraconazole in BSS, olive oil, PVA, and boric acid produced inhibition zones of 17.3, 15.6, 15.4, and 13.2 mm, respectively. Ketoconazole produced inhibition zones of 35.9, 39.4, 41.8, and 44.7 mm, respectively. From a standard curve, the concentrations of ketoconazole in tissue were 512, 773, 1221, and 1492 micrograms/g, respectively. CONCLUSION: The vehicle that is used to triturate antifungals affects the tissue concentration. This may have an impact on fungal keratitis therapy.