Prolongation of canine renal allograft survival by combining tacrolimus with antimetabolic agents.

,....-,HE SYNERGISTIC combination of immunosuppres.1 sive drugs is thought to provide a better therapeutic index with fewer side effects than single-drug therapy. Tacrolimus (FK 506), an inhibitor of interleukin-2 (IL-2) synthesis, is a potent immunosuppressive agent that has various adverse effects including nephrotoxicity, neurotoxicity, diabetogenesis. and infectious complications.! Experimental models have shown that antimetabolic agents are good candidates for combination with tacrolimus.2•3 Several antimetabolic agents. azathioprine (AZA). mizoribine (MIZ). mycophenolate mofetil (RS), and ethyl o-[N-(pcarboxyphenyl)-carbamoyIJ-mycophenolate (CAM), were tested alone and in combination with tacrolimus to determine if they could improve canine renal allograft survival. while reducing immunosuppression-related adverse events.