Getting Tacrolimus Dosing Right.

Area of Science:

• Pharmacology and Therapeutics
• Nephrology
• Clinical Chemistry

Background:

• Tacrolimus (TAC) dosing traditionally relies on trough concentration (C0), but its correlation with clinical outcomes is limited.
• Significant inter-patient variability exists in the relationship between TAC C0 and the area under the curve (AUC).

Purpose of the Study:

• To evaluate the utility of TAC AUC monitoring, potentially replacing or supplementing C0 monitoring.
• To propose a method for estimating individual AUC/C0 ratios and deriving individualized C0 targets for TAC therapy.

Main Methods:

• Review of existing studies on TAC C0 and AUC monitoring in kidney transplant recipients.
• Discussion of Bayesian estimation and machine learning for TAC AUC assessment.
• Exploration of microsampling devices for patient-friendly TAC level collection.

Main Results:

• Observational studies suggest TAC AUC is linked to efficacy and adverse events, more so than C0.
• Current methods allow for feasibility of reaching target TAC ranges and reducing exposure extremes.
• A proposed method estimates individual AUC/C0 ratios to guide C0 targets between AUC monitoring.

Conclusions:

• Existing technology supports AUC monitoring interspersed with individualized C0 monitoring for kidney transplant patients.
• Collecting real-world data is crucial to strengthen the evidence for AUC-guided TAC dosing.
• Individualized AUC/C0 ratio estimation offers a promising approach to optimize TAC therapy.