Abstract
Purpose:
To enhance the pharmacokinetic properties of ophthalmic antimicrobials, high-concentration of active ingredient or surface-retentive delivery system are being used. However, ocular toxicity is a concern when using these agents. In this study, we evaluated the cytotoxicity of various ophthalmic antibiotics on SV40-immortalized human corneal epithelial cells using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.
Methods:
We tested original and 10-fold diluted solutions of Cravit (levofloxacin 0.5%), Cravit 1.5 (levofloxacin 1.5%), Quixin (levofloxacin 0.5%, Benzalkonium chloride (BAK) 0.005%), Iquix (levofloxacin 1.5%), Vigamox (moxifloxacin 0.5%), Moxeza (moxifloxacin 0.5%, xanthan gum), Gatiflo (gatifloxacin 0.3%), Zymaxid (gatifloxacin 0.5%, BAK 0.005%), Besivance (besifloxacin, BAK 0.01%, durasite), Azasite (azithromycin 1%, BAK 0.003%, durasite), Tobrex (tobramycin 0.3%, BAK 0.01%). We also tested using standard material powders of each drug to rule out the effect of other components in ophthalmic solutions. The MTS assay was performed after 5 to 120 minutes of exposure to each solution. According to the cell survival score, we graded the cytotoxicity as mild(over 75%), moderate(50~75%) and marked(below 50%).
Results:
Following exposure to undiluted solutions, cell viabilities were decreased to 9~73% after 5 minutes. After 30 minutes Tobrex, Zymaxid and Quixin showed marked toxicity, Cravit 1.5, Iquix and Vigamox showed moderate toxicity and Cravit and Gatiflo showed mild toxicity. When exposed to 10-fold diluted solutions, Tobrex, Besivance, Zymaxid, Quixin and Azasite, which were BAK containing products, showed moderate toxicity. After exposure to standard powder solutions, 0.6% besifloxacin, 0.5% gatifloxacin, 0.5% moxifloxacin, 1.5% levofloxacin and 0.5% levofloxacin showed moderate toxicity in decreasing order. However, 1% azithromycin and 0.3% tobramycin standard powder solutions showed the least toxicity.
Conclusions:
High concentration alone did not further increase cytotoxicity. The most important factor for the determination of cytotoxicity was the concentration of BAK in antimicrobial solutions.
Keywords: 422 antibiotics/antifungals/antiparasitics •
620 ocular irritancy/toxicity testing •
482 cornea: epithelium