Transl Clin Pharmacol.  2018 Jun;26(2):56-59. 10.12793/tcp.2018.26.2.56.

Pharmacodynamic principles and the time course of delayed and cumulative drug effects

• Holford N

• KMID: 2413827
• DOI: http://doi.org/10.12793/tcp.2018.26.2.56

Abstract

This tutorial reviews the principles of the concentration "” effect relationship for the usual case when drug effects are delayed relative to changes in circulating concentrations. The key processes determining delay are distribution from the circulation to the receptor, binding to the receptor to produce a stimulus and translation of the receptor stimulus into an effect through turnover of physiological mediators. Some clinical outcomes are dependent on the accumulation of drug action which is predictable in terms of basic pharmacokinetic and pharmacodynamic concepts.

Keyword

Cumulative response; Delayed of drug effect; Receptor binding; Turnover models

MeSH Terms

Dose-Response Relationship, Drug
Models, Biological

Figure

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  Figure 1 Thiopental time course of plasma concentration (Cp) and effect on EEG (after [1]).

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  Figure 2 The effect compartment model. Cp=plasma concentration, Ce=effect compartment concentration; V=central compartment volume; CL=clearance from central compartment; T1/2,eq=equilibration half-life.

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  Figure 3 Warfarin time course.

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  Figure 4 Furosemide diuretic effect.

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  Figure 5 The time course of furosemide concentration and effect after a single large dose.

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  Figure 6 The time course of furosemide concentration and effect after a single large dose or a single small dose.

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  Figure 7 The time course of furosemide concentration and effect after a single large dose or three small doses.

Reference

1. Stanski DR, Maitre PO. Population pharmacokinetics and pharmacodynamics of thiopental: the effect of age revisited. Anesthesiology. 1990; 72:412–422.

2. Weiss M, Kang W. Inotropic effect of digoxin in humans: mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding. Pharm Res. 2004; 21:231–236.