Solid organ transplant recipients are reliant upon a combination of lifelong 1 immunosuppressant medicines to maintain functioning of their grafts. Therapeutic drug 2 monitoring (TDM) is a well-established approach for guiding therapy, which involves 3 individualization of drug dosage by maintaining drug concentrations within a pre-defined 4 target range. TDM is routinely performed during treatment with calcineurin-and mTOR 5 inhibitors and is sometimes undertaken during mycophenolate usage. Consensus reports 6 have established optimal TDM practices for these agents (Brunet et al., 2019;Shipkova et 7 al., 2016;Bergan et al., 2021). While few studies have assessed the clinical benefits of TDM 8 in a prospective, randomised manner, several studies have demonstrated a correlation 9 between low immunosuppressant exposure and risk of acute rejection and high 10 immunosuppressant exposure and drug toxicity.
For practical and economic reasons, TDM is frequently based on a single time-point 12 measure, often the morning trough concentration. The time-of-day monitoring is performed 13 may have implications for immunosuppressant medicines dosed more than once-a-day. (Staatz et al., 2011;Brooks et al., 23 2021). While in its infancy machine learning techniques are also starting to be applied to 24 predict AUC (Wollard et al., 2021a;Wollard et al., 2021b).
