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Review Article
1 April 1996

Scaling basic toxicokinetic parameters from rat to man.

Publication: Environmental Health Perspectives
Volume 104, Issue 4
Pages 400 - 407


Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinical trials of investigational new drugs. Current strategies for scaling either doses of xenobiotics or the dispositional parameters of xenobiotics from animals to man rely on models that take account principally of species differences in weight or body surface area. Interspecies scaling of dispositional parameters such as clearance or volume of distribution commonly involves the comparison of estimates of these parameters for a given xenobiotic among numerous species on the basis of weight with the resultant mathematical relationship used to predict the values of those parameters for that xenobiotic in a species weighing, on average, about 70 kg (i.e., a man). Our approach has been to ascertain whether a useful mathematical model could be developed for predicting the dispositional parameters of a xenobiotic, its half-life and volume of distribution, in humans based exclusively on estimates of those parameters in rats. Based on a data set of about 100 different xenobiotics, we found that values for half-life and volume of distribution of a xenobiotic in humans can be predicted from the estimates of those parameters in rats.

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Published In

Environmental Health Perspectives
Volume 104Issue 4April 1996
Pages: 400 - 407
PubMed: 8732950


Published online: 1 April 1996



K Bachmann
Department of Pharmacology, University of Toledo, OH 43606, USA.
D Pardoe
Department of Pharmacology, University of Toledo, OH 43606, USA.
D White
Department of Pharmacology, University of Toledo, OH 43606, USA.

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