Comparison of cyclophilin binding assay and radioimmunoassay in monitoring of blood cyclosporine

Cyclosporine binds with cyclophilin, an abundant protein found in almost all tissues, and the resulting complex interacts with calcineurin diminishing T-cell activation. Cyclophilin can be regarded as a cellular ''receptor'' for cyclosporine. Measuring cyclosporine binding to cyclophilin may offer a link between pharmacokinetics and pharmacodynamics that could improve monitoring of cyclosporine therapy. The authors investigated the feasibility of the cyclophilin binding assay and compared the results with a standard specific monoclonal radioimmunoassay in 100 blood samples taken for therapeutic drug monitoring. The results obtained with these methods were related closely with each other (r = 0.96; p < 0.001) but the mean (+/-SEM) concentrations were approximately two-fold higher in cyclophilin binding assay than in radioimmunoassay (520.4 +/- 49.9 ng/ml versus 257.7 +/- 28.6 ng/ml, respectively, p < 0.001). The shapes of the cyclosporine concentration versus time curves in two patients after a liver and heart transplantation, respectively, were similar after both methods but cyclophilin binding assay gave higher values than radioimmunoassay. Before firm conclusions on the clinical value of cyclophilin binding assay can be made, comparative studies in patients linking cyclosporine concentrations measured with cyclophilin binding assay and standard methods to the therapeutic outcome are needed.