Background: Tacrolimus exposure is estimated by trough levels (C0). Recent studies suggest that C0 may not accurately reflect the area under the curve (AUC) and may not correlate with clinical events like acute rejection (AR) and nephrotoxicity. Materials and Methods: In an open, prospective, single-center study, 29 consecutive recipients of renal transplantation underwent C0 along with 2-h (C2), 4-h (C4), and 6-h (C6) estimation of blood tacrolimus levels by enzyme-linked immunosorbent assay, 72 h after initiation with tacrolimus or after a change in its dosage. AUC was estimated by trapezoidal method. C0, C2, C4, and C6 levels were correlated with the AUC. Results: Thirty-six AUC estimations were made over a 2-year period. The best correlate was C6. Correlation coefficients were C0 - 0.868, C2 - 0.788, C4 - 0.839, and C6 - 0.904. C6 values accounted for 79% of the variability of the AUC. Six patients experienced AR, with 5 having C0 within the target range. C6 values correlated best with AUC in these patients (C0 - 0.970, C2 - 0.833, C4 - 0.942, and C6 - 0.970). This was statistically significant. Three patients developed tacrolimus toxicity. In these patients, the correlation coefficients were C0 - 0.551, C2 - 0.556, C4 - 0.77, and C6 - 0.941. By regression analysis, we developed predictive equations. The equation AUC = 12.126 + 2.81 × C0 + 2.92 × C6 best predicted the AUC. Conclusions: Overall C6 levels were more predictive of the AUC, accurately predicting AR and nephrotoxicity. Incorporating C6 may improve tacrolimus therapeutic drug monitoring.
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