PMID: 8972106Dec 1, 1996Paper

Interspecies extrapolation of physiological pharmacokinetic parameter distributions

Risk Analysis : an Official Publication of the Society for Risk Analysis
K H Watanabe, F Y Bois

Abstract

Three methods (multiplicative, additive, and allometric) were developed to extrapolate physiological model parameter distributions across species, specifically from rats to humans. In the multiplicative approach, the rat model parameters are multiplied by the ratio of the mean values between humans and rats. Additive scaling of the distributions is defined by adding the difference between the average human value and the average rat value to each rat value. Finally, allometric scaling relies on established extrapolation relationships using power functions of body weight. A physiologically-based pharmacokinetic model was fitted independently to rat and human benzene disposition data. Human model parameters obtained by extrapolation and by fitting were used to predict the total bone marrow exposure to benzene and the quantity of metabolites produced in bone marrow. We found that extrapolations poorly predict the human data relative to the human model. In addition, the prediction performance depends largely on the quantity of interest. The extrapolated models underpredict bone marrow exposure to benzene relative to the human model. Yet, predictions of the quantity of metabolite produced in bone marrow are closer to the human model ...Continue Reading

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Citations

Jun 7, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·L P Balant, M Gex-Fabry
Jul 30, 2003·Clinical Pharmacokinetics·Ivan Nestorov
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Feb 5, 2009·Risk Analysis : an Official Publication of the Society for Risk Analysis·Aki NakayamaShinsuke Morisawa
Mar 21, 2012·Journal of Veterinary Pharmacology and Therapeutics·S ModricC Thompson
Jun 4, 2015·Journal of Toxicology and Environmental Health. Part a·Mouna Cheikh RouhouSami Haddad
Dec 20, 2011·Regulatory Toxicology and Pharmacology : RTP·Sean M HaysLesa L Aylward

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