(Bousquet-Me ́lou et al. 2004 ) and thereby give rise to undesirable sub-therapeutic
concentrations in both treated and untreated animals. A further consequence is the
occurrence of unexpected drug residues in edible tissues of untreated cattle and in
underexposure of treated animals, which may be a factor in the development of drug
resistance. It must also be stressed that the relatively poor and erratic bioavailability
of pour-on formulations has led to an increase in the dose of ivermectin, doramec-
tin, and moxidectin by a factor of 2.5 compared with subcutaneous administration,
thereby contributing to an unavoidable increase in the environmental burden for the
parent drug. Environmental issues are addressed in the chapter, “Veterinary Med-
icines and the Environment” of this text.
The influence of licking or analogous behaviour such as grooming in cats
deserves attention for topically applied drugs and may explain unexpected inter-
species differences. For example, it was shown for selamectin, a semi-synthetic
avermectin agent primarily used to kill adult fleas and ticks, that the absolute
bioavailability was only 4.4% in dogs vs. 74% in cats. In addition, the peak plasma
concentration was 63 times higher in cats than in dogs, suggesting that a major
fraction of the dose was ingested during grooming (Sarasola et al. 2002 ). In goats, a
non-licking species, the absolute bioavailability of ivermectin after a pour-on
formulation is likely to be very low (about 4–8%), as estimated approximately
from published IV AUC (Gokbulut et al. 2008 ; Gonzalez et al. 2006 ) and pour-on
AUC (Scott et al. 1990 ) data. The cause of the low systemic availability of pour-on
formulations in goats remains unclear but the lack of licking behaviour, as seen in
cattle, may be a partial explanation.
7 Consequence of Coprophagia on Drug Disposition
and Responses
Coprophagia is another individual and social behaviour phenomenon specific to
veterinary medicine. It comprises the consumption of faeces by animals. Many
domestic species such as horses, pigs, and dogs either regularly or occasionally
practise coprophagia (Soave and Brand 1991 ). In contrast, some species including
goats (at least in an unconfined grazing system) will almost always reject any plants
contaminated with the scent of their own species’ urine or faeces. Coprophagy may
lead to drug transfer between animals (allocoprophagy) or drug recycling when an
animal re-ingests its own faeces (autocoprophagy) or its own manure. The faeces of
treated foals may contain extremely high concentrations of antibiotics especially
for drugs with poor oral bioavailability. If such contaminated faeces are ingested
by an adult horse, ingested concentrations of antimicrobial drugs may suffice to
disrupt the normal adult colonic microflora, which are exquisitely sensitive to some
antibiotics.
In Sweden, it was shown that mares practising coprophagia with their foal faeces,
while the foals were receiving erythromycin for the treatment ofRodococcus equi,
had a high incidence of colitis (Baverud et al. 1998 ). Adult horses may eat manure.
Species Differences in Pharmacokinetics and Pharmacodynamics 33