Getting Tacrolimus Dosing Right.

Abstract: Tacrolimus (TAC) dosing is typically guided by the trough concentration (C0). Yet, significant relationships between TAC C0 and clinical outcomes have seldom been reported or only with adverse events. Large retrospective studies found a moderate correlation between TAC C0 and the area under the curve (AUC), where, for any given C0 value, the AUC varied 3- to 4-fold between patients (and vice versa). However, no randomized controlled trial evaluating the dose adjustment based on TAC AUC has been conducted yet. A few observational studies have shown that the AUC is associated with efficacy and, to a lesser extent, adverse effects. Other studies showed the feasibility of reaching predefined target ranges and reducing underexposure and overexposure. TAC AUC0-12 h is now most often assessed using Bayesian estimation, but machine learning is a promising approach. Microsampling devices are well accepted by patients and represent a valuable alternative to venous blood sample collection during hospital visits, especially when a limited sampling strategy is required. As AUC monitoring cannot be proposed very frequently, C0 monitoring has to be used in the interim, which has led to fluctuating doses in patients with an AUC/C0 ratio far from the population mean, because of different dose recommendations between the 2 biomarkers. We proposed estimating the individual AUC/C0 ratio and derived individual C0 targets to be used in between or as a replacement for AUC monitoring. Existing technology and evidence are now sufficient to propose AUC monitoring interspersed with individualized-C0 monitoring for all patients with kidney transplants while collecting real-world data to strengthen the evidence.