Drug Input Optimization: Bioavailability-Effected Time-Optimal Control of Multiple, Simultaneous, Pharmacological Effects and Their Interrelationships

Engineering control systems analysis and optimization techniques are developed, applied, and described with respect to their potential for providing rational approaches and quantitive criteira for such centrally important pharmaceutical problems as: (a) the evaluation and time-optimal, dynamic control of the therapeutic performance of drugs, drug products, and interacting drug combinations; (b) the optimal design of the dynamic drug release behavior of drug dosage forms; and (c) patient-individualized determination of optimal durg dosage regimens. A functional analysis approach is exemplified by the computation of a time-optimal drug input, which could be achieved by an appropriate mode of drug administration, which elicits optimally controlled time variations of drug-induced multiple, simultaneously occurring, pharmacological effects. A computer simulation is performed to exemplify the manner in which an ideally sought level of therapeutic response intensity may be achieved as rapidly as possible without exceeding predetermined safe and tolerable levels of adverse drug effects. The significance and manner of determination of “single-dose” dose-effect relationships are exemplified, and their significance with respect to patient-individualized drug dosage regimens is discussed. The manner in which time variations of drug effects can be interrelated with themselves and plasma drug levels is elucidated.