Can the Area Under the Curve/Trough Level Ratio Be Used to Optimize Tacrolimus Individual Dose Adjustment?

Abstract

The aim of this work was to evaluate, in a large data set of renal transplant recipients, the intraindividual variability of the area under the curve (AUC)/predose concentration (C0) ratio in comparison with that of AUC, C0, AUC/dose, and C0/dose. Patients with at least 2 tacrolimus AUC estimation requests were extracted from the Immunosuppressant Bayesian dose Adjustment website, and relative variations between 2 consecutive visits for the different metrics were calculated and compared. Data from 1325 patients on tacrolimus (3827 measured C0 and estimated AUC) showed that the lowest mean relative variation between 2 consecutives visits was for the AUC/C0 ratio (95% confidence interval [CI] relative fold change = -43% to 44% for AUC/C0; 95% CI, -77% to 72% for AUC; 95% CI, -82% to 98% for AUC/dose; 95% CI, -81% to 80% for C0 and 95% CI, -94% to 117% for C0/dose. The correlation between 2 consecutive requests, whether close or far apart, was also best for the AUC/C0 ratio ( r = 0.33 and r = 0.34, respectively) in comparison with C0 ( r = 0.21 and r = 0.22, respectively) and AUC ( r = 0.19 and 0.28, respectively). Regression analysis between AUC0-24 and C0 showed that for some patients, the usual C0 targets translated into some very unusual AUC values. As the AUC/C0 ratio is quite stable during large periods, individualized C0 targets can be derived from the AUC targets, and an algorithm that estimates the individualized C0 was developed for situations in which prior AUC estimates are available or not. In this study, we confirmed in a large data set that the AUC/C0 ratio yields low intraindividual variability, whereas C0 shows the largest, and we propose to calculate individualized C0 targets based on this ratio.