| Research Abstract |
Fluoroquinolones have recently playd an important role in treatment of infectious endophthalmitis because of an increase of delayd-onset endophthalmitis after cataract surgery and methicillin-resistant Staphylococcus aureus infection. Ocular toxicity of fluoroquinolones, however, is concerned from the viewpoint of its melanin-affinity. The ocular tolerance and dynamics of levofloxacin (LVFX), a new fluoroquinolone agent, were studied in the present research.
The effects of LVFX and its isomer (DR-3354) on the retina were evaluated by in-vitro electroretinogram (ERG) in albino rabbits. The ERG was unchanged during perfusion with 100 and 300muM of levofloxacin, and 100muM of DR-3354. The amplitude of the oscillatory potential was diminished with 300muM of DR-3354 and 500muM of LVFX.
The intraocular penetration of LVFX was studied in albino and pigmented rabbits after oral administration of ^<14>C-LVFX.The radioactivity of the eyeball of albino rabbits in the autoradiogram was much higher a
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t 1hr than 2 or 6hr after administration. On the other hand, the distribution of radioactivity in pigmented rabbits was similar at 1,2, and 6hr after administration. The LVFX concentration in the melanin-containing tissues such as the iris-ciliary body and the choroid-retina was significantly higher in pigmented rabbits than in albino rabbits after oral administraion. These results indicate that the intraocular pharmacokinetics of LVFX are markedly affected by its affinity for melanin.
The effects of intravitreal injection of LVFX on the ERG were studied to establish the non-toxic intravitreal dosage of LVFX.The oscillatory potential transiently deteriorated with 1000 and 2000 mug doses of LVFX in albino and pigmented rabbits. No ERG changes were observed with 200 and 500 mug of LVFX.These results indicate that intravitreal injections of 200 and 500 mug of LVFX are nontoxic to the rabbit retina.
The pharmacokinetics after an intravitreal injection of 500 mug of LVFX were studied in albino and pigmented rabbits. The intravitreal concentration of LVFX was similar in both albino and pigmented rabbits at each measuring point. The LVFX concentration in the melanin-containing tissues such as the iris-ciliary body and the choroid-retina was significantly higher in pigmented rabbits than in albino rabbits after intravitreal injection.
The effects of low-molecular-weight heparin, colchicine and interferon beta on in-vitro ERG were studied in albino rabbits. The ERG were unchanged during perfusion with 5 and 20 IU/ml low-molecular-weight heparin, 25 and 50 mu g/ml colchicine or 5000 and 10000 IU/ml interferon beta.
These results indicate that LVFX may be clinically applicable for the treatment of infectious eye disease. Less
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