The synergistic effect of low-dose cyclosporine and fluocinolone acetonide on the survival of rat allogeneic skin grafts.
Both CsA and topical FA can prolong the survival of skin allografts under the proper conditions. This study was performed to determine if there is a synergistic effect between these two compounds. Buf (RT1b) rat split-thickness skin grafts were transplanted onto the backs of Lew (RT1l) rats. The MST for the control group was 9.89 +/- 0.35 days. In rats given oral CsA, 2.5 or 5 mg/kg, daily from the second day of grafting, the MST was 16.0 +/- 1.9 and 13.6 +/- 0.4 days (blood CsA levels were 166 +/- 20 and 640 +/- 32 ng/ml at the time of rejection, respectively. Topical FA applied daily beginning 72 hr after grafting resulted in a MST of 24.1 +/- 3.6 days. When both topical FA and 5 mg/kg oral CsA were used, the allograft survival time was more than 100 days in 4 of 7 animals. When oral CsA 2.5 mg/kg was combined with topical CsA and FA, the allograft rejection was delayed until 50 days postgrafting in four of six animals. The synergistic effects of oral CsA and topical FA is significant, and thus allows for the use of a subtherapeutic dosage of each compound and provides a potentially safe means for prolonging skin allograft survival.
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D004357:Drug Synergism; D005446:Fluocinolone Acetonide / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation; D014184:Transplantation, Homologous
D003524:Cyclosporins; D005446:Fluocinolone Acetonide