Renal allograft survival in the baboon using a pretreatment protocol with cyclosporine

Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.