should be 10 times higher in donkeys. Similarly, PK data indicate that plasma
clearance is higher in the donkey than in the horse for several antibiotics, including
benzylpenicillin, ampicillin, amoxicillin, and oxytetracycline, but not aminoglyco-
sides (amikacin, gentamicin). Hence, no generalisation is possible and the PK of
each drug must be specifically investigated in the donkey i.e. the donkey should be
recognised and treated as a species in its own right [see review by Lizarraga et al.
( 2004 )].
In (1), bioavailability is likely to be the factor accounting for the greatest
interspecies difference, at least for the oral route of administration. Defining the
physiological characteristics among domestic species may help in understanding
and even predicting and managing the interspecies variability in drug bioavailability,
which includes not only anatomical and physiological factors but also behavioural
traits such as feeding pattern. However, extrapolation between species is hazardous
when veterinarians wish to apply data from man to dogs or cats. The mean
bioavailabilities in humans and dogs were compared for a series of 43 drugs with
different physicochemical and pharmacological properties and with a range of the
meanFvalues between 1.5 and 100%. The overall correlation was relatively poor
(r¼0.51), indicating that data derived in dogs may be inapplicable to man (Chiou
et al. 2000 ) andvice versa.
6 Pour-on Formulations: Dermal or Oral Route
of Administration?
The behavioural origin of interspecies differences and species-specific issues are
often overlooked in veterinary medicine, especially when drugs are investigated in
an experimental setting in which the natural behaviour is often altered, controlled or
even deliberately suppressed for convenience. This is the case for pour-on formula-
tions used in cattle. Pour-on administration is the topical application of a drug on
the skin in a liquid formulation; it is a very popular mode of administration for
endectocides (ivermectin, doramectin, eprinomectin, moxidectin). Topical admin-
istration is very convenient, without risk of tissue damage and without persistent
residues at the site of administration, in contrast to products containing the same
drugs administered by subcutaneous or intramuscular injection. However, pour-on
formulations are not and cannot be a purely topical route of administration in cattle,
under all normal husbandry conditions. In a natural environment, cattle lick them-
selves (allolicking) and lick other cattle (heterolicking). It was shown that either
expression or prevention of this physiological behaviour has a marked influence on
systemic bioavailability of ivermectin in cattle: most of the ivermectin poured
on skin was actually absorbed by the digestive tract (Laffont et al. 2001 ) and
pour-on formulations, under these conditions, were predominantly an oral rather
than a topical formulation. This explains why the systemic availability of the pour-
on drug formulation is both highly variable and unpredictable (Gayrard et al. 1999 ).
Moreover, allo-grooming might result in cross-contamination of untreated cattle
32 P.-L. Toutain et al.