Precision medicine using individualized biosimulations of drug dosing: Alzheimer's disease

Precision medicine requires the right drug at the right dose for the right patient at the right time. This study used a computational biology model of 30 metabolic and transport pathways and multiple compartments to simulate oral dosing of pioglitazone that is currently in clinical trials to delay onset of Alzheimer's disease. The Transcriptome-To-Metabolome <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TM</sup> Method was used to simulate individual human subjects by using their gene expression profiles to determine parameters for the kinetic biosimulation. The in silico plasma profiles for multiple doses matched those for in vivo results from literature. Individual ED50 values were determined on each subject for the mitochondrial pyruvate carrier bound by pioglitazone as the target. This approach will allow determination of effective dosing for individual subjects in clinical trials and patients for treatments.