Biomedical subjects

A Schumitzky

Publications and source records attributed to A Schumitzky.

3 recordsLinked to original sources

PubMed1990

Modeling, adaptive control, and optimal drug therapy.

Drug therapy, its clearly development, and the advent of pharmacokinetic models are described, from the original work of Teorell, through that of Augsberger and Kruger-Thiemer, to the present. Adaptive control of such models, long known in engineering, began in therapeutics with methods for linear and nonlinear least-squares regression, and has progressed to the Maximum Aposteriori Probability (MAP) Bayesian method. Strategies for optimal monitoring of serum concentrations are described and their clinical results briefly evaluated. Lastly, the new method of Approximate Optimal Closed-Loop (AOCL) control is described, in which the therapeutic regimen is used at the same time to probe (learn about) the patient's model approximately optimally. The new method considers the expected values of planned future serum concentrations (or other responses), in addition to the traditional measurement of past serum concentrations. This should optimize the process of learning about a patient's model while treating him at the same time.

Bayes Theorem↗

PubMed1979

A program package for simulation and parameter estimation in pharmacokinetic systems.

A set of programs is presented which has been developed for parameter estimation and simulation of models arising from pharmacokinetic applications. The programs can accommodate linear and nonlinear models with multiple inputs and multiple outputs. When the model is defined by differential equations, non-uniform repetitive dosage regimens can be handled. The model may also be entered in integrated form when single dose studies or uniform multiple dose studies are being considered. The programs employ a variable-step, variable-order integration routine to solve the model differential equations, and the Nelder-Mead simplex procedure to determine the parameter values which minimize a weighted least squares criterion. The programs have been written for an interactive time-sharing environment with the experimental data and model equations stored in files for future use.

Computers↗

PubMedDate not supplied

Simulation of linear compartment models with application to nuclear medicine kinetic modeling.

Several techniques are evaluated for solving the linear ordinary differential equations arising from compartment models. The methods involve approximating the matrix exponential of the state matrix (i.e. the transition matrix). The computational efficiencies of these techniques, together with that of a general purpose differential equation solver, are compared for several models arising from radiopharmacokinetic studies. The matrix exponential calculations are performed using both Ward's Padé approximation method and an eigenvalue-eigenvector decomposition (QR factorization) of the matrix A. These two algorithms have been incorporated as simulation options into the programs of the ADAPT package. ADAPT consists of a set of high-level programs for simulation, parameter estimation and experiment design, developed primarily for basic and clinical research modeling and data analysis applications involving pharmacokinetic and pharmacodynamic processes. The advantages and disadvantages of these simulation strategies for solving linear kinetic models within a parameter estimation setting are illustrated and discussed.

Algorithms↗