Drug Dosing Control in Clinical Pharmacology: Paradigms, benefits, and challenges

摘要

Control technology influences modern medicine through robotic surgery, electrophysiological systems (pace-makers and automatic implantable defibrillators), life support (ventilators and artificial hearts), and image-guided therapy and surgery. An additional area of medicine, suited for applications of control is clinical pharmacology, in which mathematical modeling plays a prominent role [1], [2]. Although numerous drugs areavailable for treating disease, proper dosing is often imprecise, resulting in increased costs, morbidity, and mortality. In this article, we discuss potential applications. of control technology to clinical pharmacology, specifically the control of drug dosing [3]. (See "Control Engineering and Medicine: A Fruitful Collaboration.") We begin by considering how dosage guidelines are developed. Drug development begins with animal experimentation. Promising agents are moved to human trials, which begin with healthy volunteers and progress to patients with the specific disease for which the drug is being developed. Early stages of these trials focus on safety, while the final trials usually involve administration of a placebo and different drug doses to evaluate efficacy. Efficacy is defined statistically, and aggregate therapeutic effects do not preclude the existence of individual patients for whom the drug is either not efficacious or causes side effects. If a therapeutic effect is observed, then the drug may be approved by the Food and Drug Administration (FDA). In general, the recommended dosage is the level found to be efficacious in the "average" patient. Herein lies the problem: the "average" patient does not exist.