Comparison and validation of limited sampling equations for cyclosporine area-under-the-curve monitoring calculations in pediatric renal transplant recipients.

Therapeutic monitoring of cyclosporine (CsA) by using area-under-the-concentration-time-curve (AUC) values in renal transplant recipients has been previously demonstrated to predict posttransplant clinical outcome. Two previous studies also reported that limited sampling equations could accurately determine the AUC of CsA using one to six blood concentration determinations in adults. The purpose of this study was to validate the accuracy of these equations in a pediatric population. In 18 pediatric patients who received renal allografts, three limited sampling equations, which used one, four, or five concentration time points, accurately estimated CsA AUC when compared with an actual 7- to 9-point curve. An equation that used a single concentration time point at 5 hours was unbiased and provided the best precision in calculating a 12-hour interval AUC. This equation had a mean absolute percentage error of 5.8% (95% confidence interval, 3.3 to 8.3). Equations using four or five concentration time points were found to provide estimates of AUC for a 24-hour interval AUC, with less than 10% error. These findings suggest that limited sampling models using as few as one to four concentration time points provide accurate estimations of CsA AUC in pediatric patients. The use of these limited sampling models provides the clinical advantage of lower blood sampling requirements and reduced costs associated with the monitoring of cyclosporine.