the latter purpose, the oral route is chosen because only this oral route enables large
numbers of animals (sometime several thousands) to be treated conveniently and
cheaply at the same time. For antibiotic use in livestock, the objective is commonly to
limit the progression of contagious disease in the overall population, rather than to
treat a single subject as for companion animals. Thus, the oral administration of drugs
in drinking water (e.g. in poultry) or as medicated feed (e.g. for pigs) ensures that all
animals are treated with minimum of labour. Another advantage of the oral route is
the absence of stress that may occur with individual treatments that require first
catching and then restraining and injecting animals individually. In addition, it is
important for food producing animals to avoid both tissue damage and the presence of
local residues, as is often the case for drugs administered individually by a parenteral
route, especially for the so-called long-acting/depot formulations. Typical of collec-
tive treatments are antimicrobial and antiparasitic drug classes, such as coccidiostats.
In veterinary medicine, there are two differing modalities for collective anti-
biotic administration: (a) prevention in a non-infected setting; this is a prophylaxis
at the herd level when a risk factor, such as weaning in piglets or transport in calves,
is present; and (b) treatment triggered when illness is actually recognised in a
usually small proportion (often 10%) of the animals; this is metaphylaxis, also
called prevention in the infected setting. These mass medications have been
criticised on the grounds that they inevitably increase antibiotic consumption
more than selective/individual curative treatments do and as such they favour the
emergence of antibiotic resistance. However, it should be noted that these treat-
ments are initiated in animals when they still have a low pathogen inoculum size at
the infection site, a situation in which the selection pressure of antibiotic is minimal
or absent (Ferran et al. 2009 ). The main difficulty with these collective treatments is
to guarantee an equal or similar drug exposure in all treated animals. Population PK
seeks to measure the inter-individual variability that in turn reflects variability in
feeding behaviour in a competitive environment. Figure 2 illustrates the high inter-
individual dispersion of doxycycline exposure in a sample of 215 pigs under field
conditions (del Castillo 2006 ). This is of concern for the emergence of antimicro-
bial resistance, because inter-animal variability in the level of drug exposure is a
major risk factor. This arises because under-exposure of the target pathogen in only
a few animals within a flock or herd may lead to the establishment in these animals
of a less susceptible sub-population of the pathogen that subsequently may transmit
resistance genes horizontally to the other members of the group (Lees et al. 2006 ).
4 Origin of Interspecies Differences in Drug Disposition
and Drug Action
The causes of interspecies differences in drug disposition or PK are numerous and
reflect species differences in physiological processes involved in the handling of
drugs (absorption, distribution, metabolism, and elimination, ADME). This is the
26 P.-L. Toutain et al.