Aldose reductase inhibitors (ARI's) have been shown to attenuate or prevent several complications of diabetes in animals. Tolrestat is a potent and unique ARI from Ayerst Laboratories, New York, NY. The efficacy and toxicology of tolrestat via topical ocular administration was examined. Tolrestat effectively enhanced corneal reepithelialization and was efficacious in the prevention of cataracts in the streptozotocin-diabetic rat. Ocular tissues were examined by slit lamp biomicroscopy, scanning and transmission electron microscopy, and light microscopy. Liver and kidney tissue was also examined. The presence of tolrestat was confirmed in urine, feces, and eye specimens, and quantitated in serum. There was no evidence of local or systemic tolrestat induced toxicity. Tolrestat prevented cataract formation at less than one-third the reported oral dose and at approximately one-fiftieth the associated serum concentration in rats. ED-50 and TD-50 calculations indicate that tolrestat is a relatively safe drug by topical ocular administration.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc935757 |
| Date | 12 1900 |
| Creators | Carney, Gerald R. |
| Contributors | Wimbish, Gary Harold, Carnes, James E., Harris, Ben G., Yorio, Thomas |
| Publisher | North Texas State University |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | vii, 131 leaves : col. ill., Text |
| Rights | Public, Carney, Gerald R., Copyright, Copyright is held by the author, unless otherwise noted. All rights |
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