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.
D000287:Administration, Topical; D000468:Alkalies; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D065306:Corneal Injuries; D004305:Dose-Response Relationship, Drug; D005126:Eye Burns / Q000188:drug therapy* / Q000378:metabolism; D006168:Guinea Pigs; D007213:Indomethacin / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D000468:Alkalies; D007213:Indomethacin