Lees et al. ( 1986 ), Norgren et al. ( 2000 ) and Wennerlund et al. ( 2000 ) reported that
untreated horses that were housed for several days in boxes previously allocated to
horses treated with flunixin or naproxen also eliminated the drugs. This suggests
some cross contamination via the bedding. Possible contamination by ingesting
straw contaminated by urine was also well-documented for meclofenamic acid
(Popot et al. 2007 ). Therefore, it was concluded that spurious urinary drug rebound
may lead to some positive doping tests, despite observance of the recommended
withholding time.
In dogs, coprophagia is frequent and, under experimental circumstances, treated
vs. non-treated dogs should be separated to avoid cross contamination. Food
companies produce feed additives that can be added to the animal’s food to prevent
coprophagia by making faeces unpalatable. Rabbits produce two types of faeces:
soft faeces, also named caecotroph, that are rich in proteins, vitamins etc. and
regular hard faeces. By re-ingesting caecotroph directly from the anus, the rabbit
has a second opportunity to benefit from valuable nutrient substances. Such physi-
ological recycling, that typically occurs twice each day, should be considered when
treating rabbits because any drug/metabolites eliminated/produced in the digestive
tract will be partially recycled and possibly reabsorbed in the small intestine. This
has been described for chloramphenicol. For this drug, a plasma concentration
rebound was observed 24 h after an IV administration (Guillot et al. 1988 ).
The crop of broiler chickens has been implicated as a major source ofSalmonella
contamination probably due to coprophagy (Corrier et al. 1999 ) and it was shown
that a feed withdrawal that increases coprophagy also increased contamination of
the crop by food-born zoonotic pathogens such asSalmonellaandCampylobacter
species.
8 Interspecies Differences in Drug Disposition in Relation
to Digestive Tract Physiology
After a drug administered by the oral route has been swallowed, it passes to the
stomach from the esophagus. Esophageal transit normally takes a few seconds but
the esophagus shows large interspecies histological differences with practical con-
sequences for therapeutics. Esophageal muscle is striated in fish but smooth in
birds, whilst mammals show considerable species variation in the presence of these
two types of muscle. Both layers of muscle are striated throughout the length of the
esophagus in dogs, sheep and cattle, whereas in cats the esophagus contains smooth
muscle over approximately the terminal 8% of its length and 16% for its circular
muscle. This explains why cats are prone to retain foreign bodies in the distal part of
the esophagus, including drug tablets. This may be problematic if highly acidic
medications are retained that may cause severe irritation. The more extensive
section of smooth muscle is seen in the horse. From a PD perspective, striated
esophageal muscles are paralysed by curare but unresponsive to drugs acting on the
sympathetic/parasympathetic (autonomic) nervous system, while the inverse is true
34 P.-L. Toutain et al.