cyclosporine, sparse sampling, validation, HPLC, RIA, therapeutic drug monitoring

Area under the concentration-time curve (AUC) has been advocated as a better parameter to monitor cyclosporine A than trough concentrations. U to now, more thal 100 equations to estimate AUC using a limited sampling strategy have been published, but not have been validated. Eight equations for AUC o-12h and two for AUC 0-8h were validated. Concetrations of cyclosporine A were analyzed by high-performance liquid chromatograhpy (HPLC) and a specific radioimmunoassay (RIA) method. Forty male renal transplant patients were included in the study. Blood samples were taken predose and at 0,5, 1, 1,5, 2, 3, 5, 8, and 12 hours after the morning dose when the patient was in steady state. The percentage prediction error (%pe) was used for an assessment of the performance of the equations. Mean %pe less than +/- and absolute %pe lees than 30% in 95% of predictions were considered to be acceptable. Other possibilities such as %pe less than 25%, 20ˇand 15ˇwere also tested.