Comparative and Veterinary Pharmacology

species, and humans, relatively little is known of the physiology of the thousands of
other vertebrate species. It is known that oral absorption of a particular molecule
can vary considerably within a species. Beagle and mongrel dogs have very
different antipyrine clearance (Cl) (Fig. 1 ) but exhibit only minor differences in
total body weight (Martinez et al. 2009 ). If one considers the anatomical differences
between true monogastrics (i.e., dogs and cats), hind-gut fermentors (i.e., rodents,
rabbits, and horses), fore-gut fermentors (i.e., Colobus monkeys and kangaroos),
and ruminants (i.e., sheep, cattle, and goats), the potential variations in drug
absorption are considerable.
When considering other vertebrate species, such as reptiles, drug metabolism
may be affected by prandial state, for example, in snakes and other sporadic feeding
reptiles. This mechanism allows for a minor metabolic investment of digestion to
occur after a period of fasting and energy reserve depletion; thus nutrient metabo-
lism peaks about 1 week after feeding. With variable physiological states, drug
metabolism and elimination could be affected by feeding intervals. Thus, the effect
of feeding in relation to time of dosing could greatly affect the way orally adminis-
tered pharmacological agents are absorbed by snakes. When a snake consumes a
meal, the small intestinal mucosa increases in thickness at least threefold, while the
total length of the small intestine does not change. Correspondingly, villus length
increases to twice prefeeding length, resulting in an increase in small intestine
surface area as a result of feeding. Azithromycin absorption in ball pythons is
protracted, compared to that in all mammalian species reported, on the basis of
relatively large mean absorption time (MAT) andTmaxvalues (Coke et al. 2003 ).
The gastrointestinal physiology of the snake does appear to lend itself to increased
metabolism of xenobiotics (Hunter et al. 2003 ). We hypothesized that this could be

160

140

120

100

80

AUC^60

mcg*h/mL

Greyhound (33 kg)

Allometric prediction of CI

Observed CI

Using beagle CI (mL/min/kg)

Beagle (10.5 kg) Coonhound (26.7 kg)

40

20

0

Fig. 1Relationship between observed, allometric prediction (Wb), and linear predicted (W^1 using
Beagle data) antipyrine AUC values (Martinez et al. 2009 )

Interspecies Allometric Scaling 141