Cyclosporine metabolism in patients after kidney, bone marrow, heart-lung,and liver transplantation in the early and late posttransplant periods

Cyclosporine is used in the prevention of allograft rejection. Owing to its narrow therapeutic index, regular monitoring of the whole blood levels of cyclosporine is required. We observed that immunoassays measured significan tly higher cyclosporine levels than did high-performance liquid chromatogra phy (HPLC) over time after transplantation. As cyclosporine metabolites cro ss-react even with immunoassays, this observation might be due to alteratio ns of the cyclosporine metabolism. We analyzed cyclosporine metabolite conc entrations in the early and in the late posttransplantation periods in 127 patients after kidney, bone marrow, heart-lung, and liver transplantation b y HPLC and determined whole blood levels of cyclosporine by 4 immunoassays (enzyme-multiplied immunoassay [EMIT], cloned enzyme donor immunoassay [CED IA], AxSYM [Abbott Laboratories, Chicago, IL], and TDx [Abbott Laboratories ]). Despite reduced dose, we found significantly higher cyclosporine concen trations measured by the EMIT, AxSYM, and TDx assays in various patient gro ups. These results are due to the increased metabolite/cyclosporine ratio i n the late posttransplantation period. In particular, the metabolites AMI a nd AM19 increased significantly over time in bone marrow transplant recipie nts. Therefore, cyclosporine levels measured by immunoassays should be inte rpreted with caution.