Area under the curve of tacrolimus using microsampling devices: towards precision medicine in solid organ...

Therapeutic drug monitoring of tacrolimus using trough concentration (C_min) is mandatory to ensure drug efficacy and safety in solid organ transplantation. However, C_min is just a proxy for the area under the curve of drug concentrations (AUC) which is the best pharmacokinetic parameter for exposure evaluation. Some studies suggest that patients may present discrepancies between these two parameters. AUC is now easily available through mini-invasive microsampling approach. The aim of this study is to evaluate the relationship between AUC and C_min in patients benefiting from a complete pharmacokinetic profile using a microsampling approach.

Fifty-one transplant recipients benefited from a complete pharmacokinetic profile using a microsampling approach, and their 24-h AUC were calculated using the trapezoidal method. The correlation with C_min was then explored. In parallel, we estimated AUC using the sole C_min and regression equations according to the post-transplantation days and the galenic form.

Weak correlations were found between 24-h AUC observed and the corresponding C_min (R² = 0.60) and between AUC observed and expected using the sole C_min (R² = 0.62). Therapeutic drug monitoring of tacrolimus using C_min leads to over- or under-estimate drug exposure in 40.3% of patients.

Tacrolimus C_min appears to be an imperfect reflection of drug exposure. Evaluating AUC using a microsampling approach offers a mini-invasive strategy to monitor tacrolimus treatment in transplant recipients.