Promotion of corneal allograft survival with leflunomide.
OBJECTIVE
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.


CONCLUSIONS
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.
Niederkorn
J Y
JY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235.
Lang
L S
LS
Ross
J
J
Mellon
J
J
Robertson
S M
SM
D000284:Administration, Oral; D000818:Animals; D003315:Cornea / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D015948:Keratoplasty, Penetrating; D000077339:Leflunomide; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D016572:Cyclosporine; D000077339:Leflunomide