COMPARISON OF CYCLOPHILIN BINDING ASSAY AND RADIOIMMUNOASSAY IN MONITORING OF BLOOD CYCLOSPORINE

Cyclosporine binds with cyclophilin, an abundant protein found in almo st all tissues, and the resulting complex interacts with calcineurin d iminishing T-cell activation. Cyclophilin can be regarded as a cellula r ''receptor'' for cyclosporine. Measuring cyclosporine binding to cyc lophilin may offer a link between pharmacokinetics and pharmacodynamic s that could improve monitoring of cyclosporine therapy. The authors i nvestigated the feasibility of the cyclophilin binding assay and compa red the results with a standard specific monoclonal radioimmunoassay i n 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 approximat ely two-fold higher in cyclophilin binding assay than in radioimmunoas say (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 cu rves in two patients after a liver and heart transplantation, respecti vely, were similar after both methods but cyclophilin binding assay ga ve 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 outc ome are needed.