Topical indomethacin: inhibition of corneal wound healing in guinea pigs after severe alkali burn.

Corneae of guinea pigs were burned with 200 microliters 1N-NaOH for 30 seconds. Topical application of 1%, 0.1%, or 0.025% indomethacin (IN) four times daily resulted in a marked delay of corneal re-epithelialization compared to corneae receiving the vehicle only. However, no retardation of corneal wound healing was observed when IN was injected intraperitoneally (5 mg/kg) twice daily, but hyperemia and chemosis were reduced. To study the proportion of retained IN in burned cornea, 0.1% IN was mixed with a tracer dose of [2-14C] IN: 3.4, 1.2, 0.42, and 0.24% of the dose were retained 20, 60, 180, and 360 minutes respectively after topical application of 15 microliters. Twenty minutes after application of 15 microliter 0.1% IN, the concentration of retained IN in the cornea was 31 micrograms/g, which is considerably higher than the average concentration of 0.358 microgram/ml found in human blood plasma after therapeutic doses of IN. Thus, the retardation of corneal wound healing may be explained by a cytotoxic effect of supratherapeutic concentrations of IN.