June Buell

Reduction of Digitalis Toxicity by Computer-Assisted Glycoside Dosage Regimens

Abstract Computer-assisted dosage regimens of digitalis leaf, digitoxin, digoxin, and deslanoside (Cedilanid-D®) have reduced the frequency of adverse reactions to such glycosides from 35% to 12% (...

An improved method of digitoxin therapy.

Abstract An improved method of digitoxin therapy is presented for adult euthyroid patients of average weight with normal hepatic function, electrolyte balance, and gastrointestinal absorption whose...

A computer program for digitalis dosage regimens

Abstract A computer program written for a commercial time-shared system is described, which will develop dosage regimens of four common digitalis preparations. It has been used as a telephone aid to calling physicians. Dosage regimens of digitalis leaf, digitoxin, digoxin, and Cedilanid-D are adjusted to the patients weight, renal function, route of administration, and present computed concentrations of glycoside. They will replace one glycoside with another, maintaining an essentially constant peak computed body glycoside level throughout the transition period and thereafter. The mathematical description employed are highly correlated with measured glycoside concentrations in plasma, serum, myocardium, and urine. Use of this program for the past two years has reduced adverse reactions to glycoside therapy from 31% to 12%, a highly significant difference (P

Modern control theory and optimal drug regimens, I: the plateau effect

Abstract It is assumed that the pharmacokinetics of certain drugs (digitalis drugs, sulfa drugs, etc.) are described by a model of E. Kruger-Thiemer. An initial dose and regular maintenance doses are to be given so as to achieve body levels of the drug that show neither accumulation nor depletion (the plateau effect). The suggested dose regimens are displayed in the form of nomograms.

A mathematical study of the metabolic conversion of digitoxin to digoxin in man

Abstract This article describes a mathematical study of the average rate of metabolism of digitoxin to digoxin in patients, and an improved mathematical description of digitoxin kinetics. This description closely fits observed data of pharmacological effect and urinary excretion of both digitoxin and digoxin in patients receiving USP digitoxin. It permits quantification of the effect of reduced renal function on overall digitoxin-digoxin kinetics, and should yield improved precision and safety for digitoxin therapy. Metabolism of digitoxin to digoxin appears to be a relatively minor pathway of digitoxin losses.

Modern control theory and optimal drug regimens. II: Combination therapy

Abstract In this article we show how well-known concepts from control theory are directly applicable to the problem of determining methods for administering a combination of drugs to achieve a desired level for the equivalent amount of any one of the drugs under consideration. The problem of drug administration is shown to be equivalent to a discrete-time optimal control problem. Methods for solving the discrete optimal control problem via dynamic programming are shown.

Quasilinearization and the fitting of nonlinear models of drug metabolism to experimental kinetic data

Abstract In recent years it has been shown that the biotransformation of various drugs in the therapeutic dose range is not adequately described by linear models. For enzymatically mediated reactions, for example, the phenomena of saturation and substrate depletion lead to nonlinear effects. A basic task is to fit nonlinear theoretical models to observed data for various metabolic processes. This is done for a process involving Michaelis and Menten kinetics. A numerical experiment is described, and various extensions are suggested.

Exact Solution of a Family of Matrix Integral Equations for Multiply Scattered Partially Polarized Radiation. II

In the theory of multiply scattered partially polarized radiation, a key role is played by the integral equation J(t,x,z)=Ie−(x−t)/z+ ∫ 0xK(|t−y|)J(y,x,z)dy, 0≤t≤x, where J and K are square matrices, I is the unit matrix, z is a parameter lying in the interval (0, 1), and for the interval length x, 0 ≤ x ≤ x1. It is shown that this family of matrix integral equations can be transformed into a Cauchy problem that is readily solved by modern computing machines.

Numerical results for a mixed boundary-value problem of potential theory using invariant imbedding

Abstract A mixed boundary-value problem of potential theory is solved numerically. The problem is reduced to the solution of an integral equation using the theory of dual integral equations. The invariant imbedding treatment of that integral equation leads to the solution of an initial-value problem in ordinary differential equations. Numerical results are presented and discussed.

Identification of linear systems using long periods of observation

A new method is presented for identifying parameters in a linear differential system arising, e.g., from compartment models in drug kinetics. The linearity of the system is used to produce a series of recurrence relations that help reduce the computational load. The method is especially useful when a long period of observation is used to identify the parameters. Numerical experiments are described.