conclusion holds for birds (Hunter et al. 2008 ). For a review including applications to
veterinary species, see Mahmood ( 2005 ) and Hunter’s Chapter of this book.
Physiologically based pharmacokinetic modelling (PBPK) is another approach
to the extrapolation of data from one species (usually a major species) to another
(usually a minor species). A key element in this type of model is to make explicit
the biological system-specific properties i.e. anatomical, physiological, and bio-
chemical factors determining the disposition of the drug in question. Then, trans-
position of the values of parameters (as, for example, blood flow, organ weights,
tissue/serum partition, orin vitroestimated metabolic rate) from the known species
to a second species enables a simulation to be carried out of what might be the drug
disposition profile in the second species. Another application of PBPK to
food animals is prediction of the rate of depletion of residues from edible tissues
(Craigmill 2003 ).
3 Origin of Interspecies Differences in Modalities
of Drug Administration
Differences in the modalities of drug administration across species result from
anatomical, physiological, and/or behavioural differences. It may also depend on
animal and management husbandry procedures, as in the case for food-producing
animals, for which treatments are often collective. In cattle, the udder has a single
large teat canal for each quarter leading to a single large teat cistern and this enables
the entire mammary quarter to be treated conveniently by intramammary infusion.
In horses, intramammary infusion is also possible but it should be considered that
each teat has two streak canals leading to two separated lobulo-alveolar tissue
systems with no communication between the two halves of the udder. In dogs,
the nipples have several fine openings (7–16) preventing local drug administration.
Intramuscular administration is a popular modality of drug administration in
veterinary medicine and apparently no major differences exist across species in
their skeletal muscular systems, so that no major differences are expected between
species for the bioavailability of intramuscularly injected drugs. In poultry, how-
ever, the site of administration should be carefully selected (generally the pectoral
muscle is chosen), because the bioavailability of a drug injected into the leg can be
low or even null due to a first-pass effect in the kidney. This is because the kidney in
birds is of a reptilian type with a renal portal system draining the lower regions of
the body. Reptiles should also be injected in the anterior portion of the body when a
drug is eliminated by the kidneys (Hunter 2009 ). For subcutaneous administration,
it is reasonable to assume considerable similarity between species regarding the
local tolerance of formulations. However, it should be noted that cats are specifi-
cally prone to the development of localised fibrogranulomatous reactions to inject-
able vaccine products, producing vaccine-induced sarcomas as a result of malignant
transformation of the fibroblastic cells associated with the prolonged inflammatory
reaction (Se ́guin 2002 ).
24 P.-L. Toutain et al.