RELATIONSHIP BETWEEN RATE OF ELIMINATION OF TUBOCURARINE AND RATE OF DECLINE OF ITS PHARMACOLOGICAL ACTIVITY BY

It is shown on theoretical grounds that, assuming tubocurarine elimination is an expo-nential process and the intensity of its pharmacological activity is proportional to the logarithm of the dose, the decline of activity is likely to be linear with time. This con-clusion is supported by clinical data. The design of rational dosage schedules of tubo-curarine to obtain sustained muscular relaxation has recently been described by Ryan (1964). His paper dealt primarily with the time course of tubocurarine concentration or amount in the body; it is intended here to consider the time course of tubocurarine activity. Let it be assumed that the intensity of phar-macological activity of tubocurarine is related linearly to the logarithm of the body drug content (dose). This is a common finding with most drugs and applies over a considerable range of pharma-cological activity. In mathematical terms I = ni \o%A + i (1) where / is the intensity of pharmacologic activity, A is the amount of tubocurarine in the body, m is the slope of the line when I is plotted against log A, and t is the intercept of the line on the / axis. Assuming exponential disappearance of tubo-curarine from the body, logA=logA0- — t (2) where A is the amount of tubocurarine in the body at time t, Ao is the intercept at zero time of the extrapolated linear portion of a plot of log A versus t, and K is the first-order elimination rate constant for tubocurarine. Equations (1) and (2) may be combined (Levy, 1964) to yiel