Integrated PK/PM Model-based Medication Dosing Assist App(lication) in KlinischWerkStation (KWS). Validation Studies of Tacrolimus in (Solid) Organ Transplantation

The use of PK/PM model-predictive control (MPC) for guiding drug dosing at thepoint-of-care (in electronic medical file/prescription), based on population pharmacokinetic (PopPK) and pharmacometric PK models (PM), that take into accountgenetic, demographic, biological and other (bio)marker parameters that influence ADME(Absorption, Distribution, Metabolism, Elimination) of narrow therapeutic drugs, can support clinicians in determiningthe optimal dose adaptations inroutineclinical practice.With model-based dosing support or dosing assistance, quality of clinical care can be broadly improved:a) Faster achievement oftarget therapeutic concentrations rangesb) Attenuation of “off-target concentrations”(sub- and supra-therapeutic)c) Reduction of intra-patient variability (IPV)in drug exposured) Optimizingtiming of concentration measurements 4e) More accurate dose adjustments in the presence of known (and unknown) inhibitors / inducers of tacrolimus ADME (drug-drug interactions; DDI)f) Potential pharmaco-economicadvantageg) Improved drug tolerance /quality of life patients (less adverseeffects)h) Optimization of clinical workflow (automation clinical decision tree in KWS)i) Improved patient safety (traceable validated decisionprocess)j) Support, education and (learning) feedback for medical traineesk) Continuous process optimization through machine learning.We seek to implement the tacrolimus dosing assist app (Tdmore)at the point-of-carein different clinical applications including solid organtransplantation,bone-marrow transplantation and inflammatory/ autoimmune diseases. Currently, the proof-of-concept was established in the UZ Leuven KWS for tacrolimus dosing assist in kidney transplantation (validation ongoing).

Keywords:Immunosuppressive drug dosing, Therapeutic Drug Monitoring, PopPK/PM modeling, Drug dosing assist applications, Artificial Intelligence

Disciplines:Pharmacotherapy