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Aspects of the relationship between drug dose and drug effect.

Authors
  • Peper, Abraham1
  • 1 Department of Medical Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. [email protected] , (Netherlands)
Type
Published Article
Journal
Dose-response : a publication of International Hormesis Society
Publication Date
Feb 09, 2009
Volume
7
Issue
2
Pages
172–192
Identifiers
DOI: 10.2203/dose-response.08-019.Peper
PMID: 19543483
Source
Medline
Keywords
License
Unknown

Abstract

It is generally assumed that there exists a well-defined relationship between drug dose and drug effect and that this can be expressed by a dose-response curve. This paper argues that there is no such clear relation and that the dose-response curve provides only limited information about the drug effect. It is demonstrated that tolerance development during the measurement of the dose-response curve may cause major distortion of the curve and it is argued that the curve may only be used to indicate the response to the first administration of a drug, before tolerance has developed. The precise effect of a drug on an individual depends on the dynamic relation between several variables, particularly the level of tolerance, the dose anticipated by the organism and the actual drug dose. Simulations with a previously published mathematical model of drug tolerance demonstrate that the effect of a dose smaller than the dose the organism has developed tolerance to is difficult to predict and may be opposite to the action of the usual dose.

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