wherePmetis the metabolic power (rate of O 2 consumption if considered equivalent
to the energy metabolism per unit time), 70 is the “ideal” body weight of an adult
human,Mis body mass, and 0.75 is the slope of the regression Kleiber used to make
the mathematical calculation easier in the time period prior to the introduction of
handheld calculators (Schmidt-Nielsen 1984 ).
Kleiber reported wide ranges of body weight and heat production within species,
such as the humans, dog, and horse. The observations that body size and physio-
logical processes are scalable by allometric equations were later summarized by
Schmidt-Nielsen ( 1984 ). Various physiological processes, such as heart rate, blood
volume, and glomerular filtration rate appeared to be predicted accurately for a
wide variety of species, solely on the basis of the weight of the animal. Thus, body
weight is generally considered to be the most predictive for allometric scaling,
when raised to some exponent. From this observation, it can be reasoned that,
because drug pharmacokinetic profiles are ultimately regulated by physiological
functions, pharmacokinetic variables and parameters and the corresponding
dosages would also follow a similar allometric scaling trend relative to body
weight.
2.1 Linear Extrapolation
Linear extrapolation is the use of a single mg/kg dose established for one species
and applied across all species, so that the total amount of drug increases in a linear
fashion as body weight increases. For a given drug, a combination of pharmacoki-
netic and efficacy studies is performed to select an optimal dose for a specific
species, in order to obtain an approved label claim. This method is commonly used
for the target species throughout the typical weight range for the species. Given that
this weight range in the dog can vary by an order of magnitude (Martinez et al.
2009 ), there is great potential to overdose or underdose at the extremes. The
advantage of this system is the simplicity of the calculation and standardization
of a single dosage for the species. However, problems may arise when this method
is applied to other species without regard to species-specific pharmacological
differences or to the weight range of the unapproved species (Mahmood et al.
2006 ; Martinez et al. 2006 ). The underlying assumption of this method is that
any differences in species pharmacokinetics/pharmacodynamics (PK/PD) are not
clinically relevant.
2.2 Metabolic Scaling
Metabolic scaling uses the ratio of a known physiological process or anatomical
feature (such as basal metabolic rate or body-surface area) of two species to
estimate a dosage in a species in which there is limited pharmacokinetic data.
144 R.P. Hunter