Concentrations of three anti-infective agents in tear film were monitored after one topical application in rabbits. Ofloxacin concentrations exceeded the MIC for 90% of the organisms tested (MIC90) (gram-negative and gram-positive organisms) for 240 min. Tobramycin concentrations exceeded the MIC90 for 10 min. Gentamicin concentrations exceeded the MIC90 for 20 min for gram-positive organisms and 120 min for gram-negative organisms.The increasing number of bacterial strains resistant to widely used antibiotics has given impetus to the search for new anti-infective agents, including drugs suitable for topical use in the treatment of ocular infection. The fluoroquinolones are a class of compounds possessing bactericidal activity against gram-negative and gram-positive organisms and some anaerobic bacteria. Ofloxacin is a fluoroquinolone that shows promise in treating ocular infections (1, 2). Ofloxacin is active against a broad spectrum of bacterial organisms (9), including many species isolated from ocular sources (4, 5, 10-15). Bacterial resistance to ofloxacin rarely arises, and ofloxacin-resistant strains are generally unable to compete with nonresistant strains (4, 7).The value of ofloxacin in treating ocular infections depends in part on the maintenance of effective concentrations in the eye for sufficient periods. The MIC against 90%o of bacterial strains tested in vitro (MIC90) of an anti-infective compound is a useful gauge of effective concentration. In this study, the durations at effective concentrations of ofloxacin and the commonly used aminoglycosides gentamicin and tobramycin were determined.(Results of this study were reported as a poster presentation at the 61st Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla., May 1989.) Drug concentrations were measured at multiple time points after a single topical application. The test formulations were 0.3% ofloxacin, 0.3% gentamicin (Genoptic Liquifilm; Allergan Pharmaceuticals, Irvine, Calif.), and 0.3% tobramycin (Tobrex Solution; Alcon Laboratories, Fort Worth, Tex.). Healthy female New Zealand albino rabbits (Vista Rabbitry, Vista, Calif.) weighing approximately 2.0 to 3.5 kg were each treated with 50 IL oftest formulation placed in the lower conjunctival cul-de-sac of the left eye with a micropipette. After drug application, the eyelids were held closed for 30 s.Tear samples were collected from the lower conjunctival cul-de-sac with a Schirmer strip before treatment and from 1 to 360 min after treatment. At each time point, tear specimens were obtained from 10 rabbits and specimen weights were recorded. The Schirmer strips containing tear samples were dried immediately under a stream of N2 and stored at -20°C until they were assayed. Ofloxacin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorometric detection. Samples were introduced into the HPLC system with an Intelligent Sample Processor (model 710B; Waters Associates, Inc., Milford, Mass.). Aqueous solvent consis...

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The objective of this study was to explore the relationship between lipophilicity and the lenticular uptake of radiolabeled xenobiotics. The lenticular uptake of amino acids was also investigated. An organ-culture technique was employed and the partitioning of compounds into the rabbit lens was measured for compounds with log octanol/water partition coefficients (log P o/w) ranging from -1 to 7.3. Drug distribution in the lens was expressed as the concentration ratio of that in the lenticular section (capsule/epithelium, cortex, and nucleus) to that in the incubation medium, (Ciens section/cm)•

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