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  • Title: Comparative bioavailability and efficacy of fortified topical tobramycin.
    Author: Gilbert ML, Wilhelmus KR, Osato MS.
    Journal: Invest Ophthalmol Vis Sci; 1987 May; 28(5):881-5. PubMed ID: 3570696.
    Abstract:
    Topical treatment of severe ocular infections may require the use of antibiotics fortified in concentration beyond commercially available preparations. The authors studied tear pharmacokinetics, tissue bioavailability, epithelial toxicity, and comparative antibacterial efficacy of topical tobramycin concentrations ranging from 0.3-5.0%. Tear pharmacodynamics demonstrate bioassay-measurable levels with each preparation up to 6 hr after a single 50-microliter drop challenge. Comparing various fortified concentration levels yields progressive parallel-biphasic decay curves in antibiotic tear-film concentrations. Both tear and corneal data demonstrate increases in measured antibiotic levels largely proportional to the increases in drug concentration instilled. Tobramycin was undetectable in corneas treated with 0.3% tobramycin, yet measurable with higher drug levels. A rabbit epithelial wound-healing model demonstrated progressive toxicity ranging from no effect of 0.3% tobramycin on healing rates compared with paired controls, to a significant decrease in re-epithelialization rates with 1.1% (P = 0.03) and 4.0% (P = 0.02) tobramycin. Finally, a Pseudomonas aeruginosa keratitis model in the rat demonstrates the antibiotic efficacy of topical tobramycin treatment over untreated controls (P less than 0.00001), and a progressively enhanced efficacy with increasing tobramycin concentrations is suggested. Concentration enhancement of topical ocular medication is useful in the treatment of severe ocular infection.
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