Comparative and Veterinary Pharmacology

extending application of the results in clinical cases. Clinicians should also care-
fully consider interspecies differences in the contribution of various organ systems
and differences in body composition in relation to body weight. Ideally, to ensure
the best therapeutic outcome, it is necessary to generate pharmacokinetic and
efficacy data in each zoo species that is treated (Locke et al. 1982 ). Before
extrapolation of any drug dose, the veterinarian should appreciate not only the
mathematical assumptions but also the limitations that are associated with allome-
try. Careful consideration of the available literature to understand the route of
elimination and the extent of metabolism of therapeutic agents will greatly assist
in determining allometric relationships of pharmacokinetic parameters (Table 4 ).
There is a continuing need to consider and apply methods for reducing the size and
risk of extrapolation error, as this can affect both target animal safety and therapeu-
tic response (Fig. 3 ). Data from at least one large animal (nonhuman and a body
weight>70 kg) should be included to reduce potential error (Table 3 ).
Phylogenetic relationships are of particular importance in applying allometry in
veterinary medicine (Chaui-Berlinck 2006 ). All extrapolation methods assume that
the route of elimination is similar across all species and this is not so in many
instances. This review illustrates how allometric scaling of pharmacokinetic data
can be applied, and emphasizes that extrapolations between species should not be
used to predict an appropriate therapeutic dosage regimen without careful consid-
eration of the limitations. Riviere et al. ( 1997 ) estimated that of all drugs 75% are
not scalable across multiple species.
Just as mammals can range from a few to thousands of kg, reptiles and birds
can also vary in body weight across a wide range (Table 5 ). It has been suggested

1000

y = 11.099x0.0572

R^2 = 0.0038

100

L/h^10

1

0.1

0.01 0.1 1

Body weight (kg)

Mammals CIp

10 100 1000

Fig. 3Allometric plot determined for enrofloxacin plasma clearance (Cl) based on 13 mammalian
species (Hunter and Isaza 2008 )

Interspecies Allometric Scaling 151