Table 2.

Methods to measure MNA using TDM of tacrolimus

Method	Definition	Time interval	Tac dose	Normal range	Values correlated with MNA	Limitations	Other determinants besides MNA
MLVIa [24, 25]	Tac SD of at least 3 Tac trough levels	>1 year	Changed or unchanged	<2	>2	Better used as a threshold rather than a continuous number	- Dietary preferences - High metabolizers - Drug-to-drug interactions (steroids) - Drug–food interactions - Different laboratory assays - Different Tac formulations - Clinical conditions that may increase CV independently from MNA (diarrhoea, infections, hypotension, abdominal surgery)
CV [26–28]	Tac SD/Tac mean ×100	>4–6 months (during stable phases)	Unchanged	15–30%	>50%	It is reliable only if the dose remains unchanged
Concentration/dose ratio [26]	Tac concentration (ng/mL)/Tac daily dose (mg/day) measured at steady state		Changed or unchanged	Stable within the same patients (ranging from 0.5 to 5.0 ng/mL per mg/day)	Lower than expected for each patient	Less standardized

^aPaediatrics liver transplant studies.

MNA, medication non-adherence; TDM, therapeutic drug monitoring; Tac, tacrolimus; SD, standard deviation.