title: Robust model predictive control for optimal continuous drug administration.
abstract: In this paper the model predictive control (MPC) technology is used for tackling the optimal drug administration problem. The important advantage of MPC compared to other control technologies is that it explicitly takes into account the constraints of the system. In particular, for drug treatments of living organisms, MPC can guarantee satisfaction of the minimum toxic concentration (MTC) constraints. A whole-body physiologically-based pharmacokinetic (PBPK) model serves as the dynamic prediction model of the system after it is formulated as a discrete-time state-space model. Only plasma measurements are assumed to be measured on-line. The rest of the states (drug concentrations in other organs and tissues) are estimated in real time by designing an artificial observer. The complete system (observer and MPC controller) is able to drive the drug concentration to the desired levels at the organs of interest, while satisfying the imposed constraints, even in the presence of modelling errors, disturbances and noise. A case study on a PBPK model with 7 compartments, constraints on 5 tissues and a variable drug concentration set-point illustrates the efficiency of the methodology in drug dosing control applications. The proposed methodology is also tested in an uncertain setting and proves successful in presence of modelling errors and inaccurate measurements.
authors.affiliation: School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechneiou Street, Zografou Campus, 15780 Athens, Greece; IMT Institute for Advanced Studies Lucca, Piazza San Ponziano 6, 55100 Lucca, Italy.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Sopasakis
authors.affiliation: IMT Institute for Advanced Studies Lucca, Piazza San Ponziano 6, 55100 Lucca, Italy.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Patrinos
authors.affiliation: School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechneiou Street, Zografou Campus, 15780 Athens, Greece. Electronic address: hsarimv@central.ntua.gr.
authors.forename: Haralambos
authors.initials: H
authors.lastname: Sarimveis
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D002101:Cacodylic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003198:Computer Simulation; D003879:Dermatologic Agents / Q000008:administration & dosage; D016903:Drug Monitoring / Q000379:methods*; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D007275:Injections, Intravenous; D020714:Maximum Tolerated Dose; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity; D014018:Tissue Distribution
chemical_list: D003879:Dermatologic Agents; D002101:Cacodylic Acid
keywords: Drug administration control; Drug dosing; Model predictive control; PBPK modelling