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.