Erowid References Database
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Campbell DB.
“Extrapolation from animals to man: the integration of pharmacokinetics, and pharmacodynamics”.
Ann N Y Acad Sci. 1996;801:116-135.
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Abstract
The detailed investigation on the mechanism of action or toxicity of drugs is most frequently undertaken on animals and it is assumed that the results can in some way be used to provide an understanding of the effect in man. However, comparatively little research has been done to look at the validity and predictability of the animal models used to extrapolate data to the clinical situation. There are two primary assumptions that are made: firstly, that the mechanisms involved in the effect of a compound are similar across species and secondly, that the biodisposition is the same. Increasingly it is being found that neither of these assumptions is necessarily true. Animals not only do not have the same receptors but their functions may be different and it is the role, rather than the exception, that the an/reals have different kinetic and metabolic profiles to those found in humans. Thus, comparisons of the effect of a drug in different species using dosage may, therefore, provide little information on the comparative activity. However, the difficulties do not stop there since measurement of the active moietyin circulating blood may not provide a correct measure of the levels at the active site. There are many factors which can influence the biodisposition ora drug including strain. gender, route and dosage, time of administration, coadministration of other drugs nd other investigatory manipulations. Without a knowledge of the drug levels, and perhaps some attempt to relate these levels to the activity, the interpretation and cross species extrapolation is likely to be less than precise. This paper examines the problems of predicting the effects of drugs and relating data found in animals to man and present methods which are becoming available to overcome these difficulties.
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