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Interspecies Variations in Pharmacokinetics: A Perspective

  • H. Boxenbaum
  • R. Ronfeld

Abstract

As part of the pharmacokinetic ground plan, interspecies variations are considered and treated as a property and consequence of body size (allometry) and longevity. In 10 mammalian species other than man, antipyrine intrinsic clearance of unbound drug (CLuint, liters/min) is given (1) by the following alldmetric relationship:

CLuint = 0.00816 B0.885 (1)

where the coefficient takes on appropriate units and B is body weight in kg. In these same species, liver weight (L, kg) is given by (1):

L = 0.0370 B0.849 (2)

Combining Equations (1) and (2), one obtains:

CLuint = 0.00816 (L/0.0370)0.885/0.845∼0.22 L (3)

This relationship indicates that antipyrine CLuint may be approximated as 0.22 liters/min/kg liver weight (invariant number) in all 10 mammalian species. The CLuint for man is 0.028 liters/min/kg liver weight, or about one-eighth that of other species. Similar liver weight-adjusted CLuint ratios between animals and man have been noted for phenytoin, clonazepam and propranolol. Multiplying CLuint by species maximum lifespan potential (MLP, years) gives the volume cleared per MLP, assuming constant drug exposure. The appropriate equation for antipyrine (2) is:

(CLuint) (MLP) = n(0.33 · 105) B1.09 (4)

Keywords

Mammalian Species Liver Weight Unbind Drug Time Expansion Interspecies Variation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    H. Boxenbaum, Interspecies variation in liver weight, hepatic blood flow, and antipyrine intrinsic clearance: extrapolation of data to benzodiazepines and phenytoin, J. Pharmacokin. Biopharm. 8: 165–176 (1980).CrossRefGoogle Scholar
  2. 2.
    H. Boxenbaum, Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics, J. Pharmacokin. Biopharm. 10: 201–226 (1982).CrossRefGoogle Scholar
  3. 3.
    H. Boxenbaum and R. Ronfeld, Interspecies pharmacokinetic scaling and the Dedrick plots, Am. J. Physiol. 245: R768–R775 (1983).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • H. Boxenbaum
    • 1
  • R. Ronfeld
    • 2
  1. 1.School of PharmacyUniversity of ConnecticutStorrsUSA
  2. 2.Pfizer, Inc.GrotonUSA

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