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Abstract
PURPOSE: The efficacy of the antirejection drug leflunomide was evaluated in a rat model of penetrating keratoplasty. METHODS: Corneal grafts from inbred Lewis rats were transplanted orthotopically to inbred Wistar-Furth (WF) recipients. WF rats received either Leflunomide (HWA 486), the active metabolite of leflunomide (A77-1726A), or cyclosporin A, administered orally beginning 2 days before transplantation and continuing for 30 days thereafter. Graft survival was assessed clinically three times per week, and mean survival times were determined. RESULTS: Oral administration of either leflunomide or the salt of its active metabolite resulted in a significant prolongation of graft survival time. Moreover, almost one third of the grafts survived for an additional 3 weeks, even after drug treatment was discontinued. CONCLUSION: The results indicate that leflunomide holds considerable promise as an antirejection drug for use in recipients of corneal transplants in whom cyclosporin A and steroids are contraindicated.