Effects of inflammation un the ocular pharmacokinetics of quinolones with different l1pophilicity in vitreous humor of rabbits

W. Liu, Q. Liu, A. Madu, M. Mayers, M. Vergara, M. Färber, A. Louie, M. Miller

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Abstract

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 languageEnglish (US)
Pages (from-to)S146
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Liu, W., Liu, Q., Madu, A., Mayers, M., Vergara, M., Färber, M., Louie, A., & Miller, M. (1997). Effects of inflammation un the ocular pharmacokinetics of quinolones with different l1pophilicity in vitreous humor of rabbits. Investigative Ophthalmology and Visual Science, 38(4), S146.