Limited Sampling Strategies for Predicting Tacrolimus Systemic Exposure After Adult Kidney Transplantation: A...

After kidney transplantation, therapeutic drug monitoring (TDM) of tacrolimus (Tac) relies mainly on the predose concentration (C0). However, C0 has limited ability to accurately reflect systemic Tac exposure. The area under the concentration-time curve (AUC) provides a more comprehensive measure of total systemic exposure and can be estimated using a limited sampling strategy (LSS). This review aimed to identify effective LSSs for predicting Tac AUC from 0 to 12 hours (AUC0-12) using 1, 2, or 3 blood samples collected between predose and 6 hours following administration of immediate-release Tac.

A literature search was conducted to identify studies reporting LSSs as predictors of Tac AUC0-12 in adult kidney transplant recipients. In the articles selected for review, the predictive performance of the strategies was evaluated based on the correlation between the predicted and the full reference AUC, as well as the associated bias and precision. Findings were synthesized using a narrative approach.

Nineteen studies evaluating LSSs for predicting Tac AUC0-12, involving a total of approximately 600 patients, were reviewed. Compared with C0, most single concentrations measured within 6 hours of administration demonstrated a stronger correlation with Tac AUC0-12. Most 2- or 3-concentration time-point strategies could predict Tac AUC0-12 with percentage prediction error and absolute percentage prediction error of less than 10%. Correlations of 0.99 were achieved with some strategies.

LSSs using as few as 2 or 3 concentrations obtained between predose and 6 hours after administration may estimate Tac AUC with strong predictive performance. The evidence supports the incorporation of intermittent AUC-based monitoring into TDM protocols as a complement to routine C0 measurement.