Abstract
It has been recognized for many years (Sokolow and Edgar 1950; Swisher et al. 1954) that drug effect may on occasion be directly associated with the time course of drug or drug metabolites in the circulation. Subsequently it was also noted that the relationship between drug concentration and response could be quite complex such that the temporal relationship might be difficult to discern on first examination, e.g., warfarin (Nagashima et al. 1969). Wagner (1975) has provided a review of early work on this topic. Sheiner et al. (1979a) illustrated the usefulness of an effect compartment for linking the time course of d-tubocurarine effect to the time course of plasma concentrations. In this way the delay in onset of effect relative to concentration could be explained. Methods for describing the kinetic behavior of drug effects were further systematized by Holford and Sheiner (1981). This chapter will discuss the motivations for characterizing the time course of drug effect, outline some methodological concerns, and present the various mathematical approaches for modeling active drug and placebo effects.
The views expressed in this paper are those of the authors and not necessarily those of the Food and Drug Administration.
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Holford, N.H.G., Ludden, T.M. (1994). Time Course of Drug Effect. In: Welling, P.G., Balant, L.P. (eds) Pharmacokinetics of Drugs. Handbook of Experimental Pharmacology, vol 110. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78680-8_11
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DOI: https://doi.org/10.1007/978-3-642-78680-8_11
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