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Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics

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Abstract

Interspecies variation in pharmacokinetics is considered and treated as a property and consequence of body size (allometry). Consequently, it is possible to reference (scale) pharmacokinetic parameters to the organism's individual anatomy, biochemistry, and/or physiology in such a manner that differences between species are nullified. Thus, in the mouse, rat, dog, monkey, and human, methotrexate plasma clearance always equals 133% of creatinine clearance and as such becomes invariant. Pharmacokinetic time (a variable in terms of chronological time) is shown to be a form of physiological time in which a pharmacokinetic event becomes the independent variable, e.g., disposition halflife. A relationship between pharmacokinetic time and body size is demonstrated. It is suggested that man's lesser quantitative ability to metabolize many drugs may be correlated with his enhanced longevity.

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Boxenbaum, H. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 10, 201–227 (1982). https://doi.org/10.1007/BF01062336

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