to a nondomestic species is to use a dose based on body weight (mg/kg) established
in the domestic species (i.e., dog, cat, cattle, swine, chickens, or humans). This
calculation results in a linear increase in the amount of drug administered as body
weight increases. Although quite common, this method tends to overdose large
animals and underdose small animals. A second method is similar, except that it
takes the approved dose in a specific species and makes an additional assumption
that links the dose to a physiological function or anatomical feature. Examples are
the use of basal metabolic rate or body-surface area as the basis for dose extrapola-
tion. Allometric scaling of pharmacokinetic parameters (Vdor Cl) is the final
method of dosage extrapolation between species. This is commonly used in the
human pharmaceutical industry to establish the first dosage in human drug inves-
tigations (Phase I).
The general form of the allometric equation used in scaling pharmacokinetic
parameters across animals is as follows:
Y¼aWb;whereYis pharmacokinetic parameter of interest;Wis the body weight;ais the
allometric coefficient; andbis the allometric exponent. The following method has
been used to predict drug clearance in humans as well as in large animals. The
clearance of each drug is plotted against the body weight on a log–log scale (where
logs are expressed to the base 10) and the following allometric equation is applied:
Cl¼aWb;whereWis the body weight andaandbare the coefficient and exponent of the
allometric equation, respectively (Mahmood et al. 2006 ).
2 History of Scaling
The concept of scaling relative to body size has been used as the basis for
comparison across species since the 1930s. The testVital Energeticsby Benedict
( 1938 ) appears to be the first comprehensive discussion on the topic of metabolic
scaling. Benedict’s work laid the foundation for the scaling of metabolic rates
across a wide range of species. The log–log plots of total heat production vs.
average body weight demonstrated that basal metabolic rate could be allometrically
scaled and does not scale linearly with respect to body mass (Chaui-Berlinck 2006 ).
The metabolic rate for mammals was described by Kleiber ( 1932 , 1961 ) to fit the
allometric equation
Pmet¼^70 M^0 :^75 ;Interspecies Allometric Scaling 143