PURPOSE: This study was carried out to get an insight into the ofloxacin elimination after intravitreal injection in rabbits. We also studied the effects of trauma and inflammation on the vitreous ofloxacin levels after intravitreal injection of ofloxacin. METHODS: A penetrating eye injury in the right eye was inflicted on 24 rabbits and another 12 animals were used as control. A standardized intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in half of the traumatized eyes. Ofloxacin (200 microg/0.1 ml) was injected into the midvitreous cavity of both traumatized and control right eyes, and samples were obtained at 2, 8, 24 and 48 h after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. RESULTS: Vitreous levels of ofloxacin were above the MIC(90) at 2 and 8 h in all groups for most of the common microorganisms causing endophthalmitis and also at 24 h in traumatized-infected eyes. At the second hour, the mean vitreous concentrations of ofloxacin both in traumatized and traumatized-infected eyes were lower than that in the control eyes (p < 0.05). At 8 h, the mean vitreous concentrations of ofloxacin in the traumatized and in the traumatized-infected eyes were higher than that in the control eyes (p < 0.05). At 24 h, the mean ofloxacin concentration was higher in the traumatized-infected eyes than that in control (p < 0.01) and traumatized eyes (p < 0.05), and also higher in the traumatized eyes than that in the control eyes (p < 0.05). The mean ofloxacin concentrations in the traumatized and traumatized-infected eyes were significantly higher (p < 0.01) than those in the controls at 48 h. The elimination half-life of ofloxacin in the control eyes was 5.65 h and trauma and inflammation prolonged the half-life to 9.47 and 9. 72 h, respectively. CONCLUSION: Clearance of ofloxacin is fast and appears to be reduced by trauma and inflammation. Therapeutic drug levels in traumatized-infected eyes were maintained up to 24 h. This may be an important pharmacokinetic advantage in treating endophthalmitis unless the dose used has local toxicity and allows a longer dose interval when the dose is repeated.
PURPOSE: This study was carried out to get an insight into the ofloxacin elimination after intravitreal injection in rabbits. We also studied the effects of trauma and inflammation on the vitreous ofloxacin levels after intravitreal injection of ofloxacin. METHODS: A penetrating eye injury in the right eye was inflicted on 24 rabbits and another 12 animals were used as control. A standardized intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in half of the traumatized eyes. Ofloxacin (200 microg/0.1 ml) was injected into the midvitreous cavity of both traumatized and control right eyes, and samples were obtained at 2, 8, 24 and 48 h after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. RESULTS: Vitreous levels of ofloxacin were above the MIC(90) at 2 and 8 h in all groups for most of the common microorganisms causing endophthalmitis and also at 24 h in traumatized-infected eyes. At the second hour, the mean vitreous concentrations of ofloxacin both in traumatized and traumatized-infected eyes were lower than that in the control eyes (p < 0.05). At 8 h, the mean vitreous concentrations of ofloxacin in the traumatized and in the traumatized-infected eyes were higher than that in the control eyes (p < 0.05). At 24 h, the mean ofloxacin concentration was higher in the traumatized-infected eyes than that in control (p < 0.01) and traumatized eyes (p < 0.05), and also higher in the traumatized eyes than that in the control eyes (p < 0.05). The mean ofloxacin concentrations in the traumatized and traumatized-infected eyes were significantly higher (p < 0.01) than those in the controls at 48 h. The elimination half-life of ofloxacin in the control eyes was 5.65 h and trauma and inflammation prolonged the half-life to 9.47 and 9. 72 h, respectively. CONCLUSION: Clearance of ofloxacin is fast and appears to be reduced by trauma and inflammation. Therapeutic drug levels in traumatized-infected eyes were maintained up to 24 h. This may be an important pharmacokinetic advantage in treating endophthalmitis unless the dose used has local toxicity and allows a longer dose interval when the dose is repeated.
Authors: Andrea Luaces-Rodríguez; Miguel González-Barcia; María José Blanco-Teijeiro; María Gil-Martínez; Francisco Gonzalez; Francisco Gómez-Ulla; María-Jesús Lamas; Francisco-Javier Otero-Espinar; Anxo Fernández-Ferreiro Journal: Pharmaceutics Date: 2018-05-29 Impact factor: 6.321