The pharmacological treatment of disease becomes more effective when the concentration of the administered drug in the body is held constant. This action provides for the renewed support of a research project in which the discrete algorithms for the closed-loop control of in vivo drug concentration or some physiological parameter has been developed. These algorithms are based on Integral Pulse Frequency Modulation (IPFM), in which control is in the form of small, bolus injections of the drug. Accurate and rapid identification means to estimate the parameters of various controlled plants (the plant dynamics relate drug concentration or regulated physiological parameter to drug input rate) while the closed-loop system is operating will be developed. Continuous estimates of the pharmacokinetic plant's parameters will be used to tune the controller, detect side-effects of the drug, and form a data base for particular drug's behavior in the body. An improved, finer grained nonlinear model of glucose metabolism will be developed in order to adapt the nonlinear IPFM controller previously designed to run effectively with a peripheral compartment glucose sensor. Futhermore, models will be developed for the dynamics of deep pain in humans, including neurophysiological and psychological factors, and the pharmacokinetics of opioid drugs for analgesia. A non-linear, adaptive, demand-analgesia controller will be designed for safe and efficient self-administration of analgesic drugs. The Principal Investigator has been well trained both in engineering and physiology to lead this interdisciplinary research. The Institutional support is adequate, I recommend support.
