Area-Under-the-Curve Monitoring of Cyclosporine Therapy

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Abstract
The measurement of areas under the concentration-time curve (AUC) was recently introduced as an alternative to trough level monitoring of cyclosporine therapy. The AUC is divided by the oral dosing interval to calculate an average concentration. All measurements are performed at clinical steady state. The initial evaluation of AUC monitoring showed advantages over trough level monitoring with concentrations of cyclosporine measured in serum by the polyclonal radioimmunoassay of Sandoz. This assay technique is no longer available and the following assays were performed in parallel during up to 173 AUC determinations in 51 consecutive renal transplant patients: polyclonal fluorescence polarization immunoassay of Abbott in serum, specific and nonspecific monoclonal radioimmunoassays using 3H and 125I tracers in serum and whole blood, and high performance liquid chromatography in whole blood. Both trough levels and average concentrations at steady state measured by those different techniques were significantly correlated with the oral dose. The best correlation (r2 = 0.54) was shown by average concentrations measured in whole blood by the specific monoclonal radioimmunoassay of Sandoz (3H tracer). This monitoring technique was also associated with the smallest absolute error between repeated observations in the same patient while the oral dose rate remained the same or was changed. Both allegedly specific monoclonal radioimmunoassays (with 3H and 125I tracer) measured significantly higher concentrations than the liquid chromatography. The following target values for average steady state concentrations were calculated based on correlations of the new methods with the polyclonal radioimmunoassay in serum, for which a target of 200 ng/ml had been established: specific monoclonal radioimmunoassay in serum, 144 ng/ml; nonspecific monoclonal radioimmunoassay in serum, 331 ng/ml; fluorescence polarization immunoassay in serum, 233 ng/ml; liquid chromatography in whole blood, 272 ng/ml; specific monoclonal radioimmunoassay with 3H tracer in whole blood, 372 ng/ml; and specific monoclonal radioimmunoassay with 125I tracer in whole blood, 431 ng/ml.