Purpose: Previous studies have shown that the % penetration into uninflamed eyes of systemically administered Fliioroquinolones (FQ) ranges from 5 -60% depending on lipophilicity. To determine the effects of inflammation on penetration of FQ's we characterized the phamiacokinetics (PK) of ciprofloxacin [C| and trovafloxacin |T| in the vilrcous humor of rabbits with and \\ithoul coagulase negative staphylococcal endophthalmitis Methods: Serial samples of vitreous humor were obtained from NZW rabbits using a recently described ocular PK model. Half of the animals were infected with .V. epidermidm (SE). Drug concentrations were determined using a microbiological assay, lipophilicity by octanol/watcr partitioning and protein binding by ultrafiltration. PK parameters were determined using RSTR1P. Percent penetration was determined by measuring the AUCviireous/AUCseruni from 0 - H hours following a single dose. The in vitro activities, and the minimal inhibitory concentrations [MICs] were determined by measuring growth at 18 hours in broth. Results: The lipophilicity/protein binding for C and T were 0.056/30% and 0.28/72%. Thy penetration of C into the uninflanied/inflamcd vitreous humor was 5.8%/23%; that for T was 40%/69%. Comparison of βtI/2 for C and T in the scrum and vitreous humor showed that inflammation had a greater prolongation effect on C [p t1/2=14.9h] than T1β t1/2 =2.84h]. The MIC for C/T were 0,5/0.05ug/nil. Conclusions: While inflammation significantly increased the penetration of both C and T. the relative increased penetration was greater for C. However, the excellent penetration of T both in the absence and presence of inflammation, in conjuction with its 10 fold greater activity against S cp/dcriniüis, suggests that it may be more effective than C. These studies also demonstrate the advantages of our serial sampling approach to ocular PK.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience